March 31, 2020
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Jed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Moringa & Sulforaphane Supplementation

[Rhonda]: Hello, everyone. I am 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. [Jed]: Sure. I’d be happy to. So, sulforaphane is a small molecule that
was discovered in broccoli by Paul Talalay and Yuesheng 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 was known that this occurred
in people at the time, but in cell cultures and in animals, they showed that it up-regulated
the protective enzymes, cytoprotective enzyme system known by some as the phase II enzyme
system. And, Paul then, who was one of the grandfathers
of chemo-protection and has…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 bio-technology,
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, it became obvious that it was very
difficult to predict how much sulforaphane a broccoli plant would have based on things
like smell, touch, color and 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 thio-glucose 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 glucoraphanin 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 labs 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 are 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 had the highest
amount on a per gram basis of glucoraphanin. But at the time, no one had eaten broccoli
seeds. You know, 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 up-regulates the protective enzymes in those cells. And so that’s why it’s so special. [Rhonda]: Like a hormetic effect, like a hormetic
effect where… [Jed]: Yeah. So clearly, if all you ate was sulforaphane,
you’d be in trouble. [Rhonda]: Yeah. [Jed]: But the same with just about anything
you can suggest. So it gears up or cranks up the protective
mechanisms of the cells. [Rhonda]: And one of those, I guess, one of
the main protective mechanisms would be the Nrf2 pathway. [Jed]: Yeah. So I have a feeling that sulforaphane would
be just be 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, in 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 up-regulating 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 and Paul Talalay,
Albena Dinkova-Kostova all at Hopkins, Masi Yamamoto in Japan, John Hayes in England,
excuse me, and I’m certainly leaving out a few people, but 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. [Rhonda]: Wow. I didn’t realize it’s that much. [Jed]: Yeah. And why is it important? It’s important because it recognizes molecules
like sulforaphane through a system, a bio-chemical 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’s actually a chaperone protein
that’s in the cytoplasm. It’s called Keap1. 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 up-regulates the antioxidant response element which is responsible for
the transcription, for initiating transcription of a whole series of protective genes or genes
in coding for a bunch of protective enzymes. And this happens very quickly, this protective
response, and its quite efficient. So to get back to sulforaphane, so sulforaphane
was discovered and then everybody started searching for the mechanism by which it acted. The Keap1-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 in 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 up-regulate protective
enzymes. You know, when I give lectures to students,
I frequently make, point out to them how they’re doing this glucoraphanin into sulforaphane
conversion, so I will 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, has a lachrymating effect. So what you are doing is you’re acting like
that insect that I told you lands on a 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 glucoraphenin in radishes. It happens to be more of a lachrymator. It’s got a more mucus-inducing effect in people. And you’re letting myrosinase in those radish
tissues act on glucoraphenin 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. [Rhonda]: Does sulforaphene also activate
Nrf2? [Jed]: It does, but to a lesser degree than
sulforaphane. [Rhonda]: So many of these isothiocyanates
also activate Nrf2, but not to the same degree as sulforaphane? [Jed]: They do. And just in case you’re about to ask me, you
find this system, it’s been dubbed the mustard oil balm by some, 20 or 30 years ago. You find this system almost exclusively in
cruciferous vegetables, or brassica vegetables or cold crops, they’re sometimes called, depending
upon where you come from, where you hail from. In Eastern Europe, they typically call them
cold crops. So this happens to be a very large family
of, I don’t know, 500 or 600 genera, many, many thousands of species. [Rhonda]: Yeah, I know, like, maybe 10 of
them. [Jed]: Well, we know maybe 20, but, I mean,
there are very many of them. And they grow worldwide although the brassica
or the cold 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 a freeze in the winter. There are some interesting relatives we can
talk about later or now if you 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. [Rhonda]: Right, okay. Yeah, maybe we can get to that little bit
later, but talk a little bit more about the sulforaphane in the broccoli sprouts. I wanted to ask you something because you
mentioned, it really piqued my attention, as you said that broccoli seeds actually had
higher amount of glucoraphanin than the sprout. If I were to say take those broccolis, 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? [Jed]: You bet. [Rhonda]: So I could actually get a higher,
more potent amount of sulforaphane theoretically if I were to just take the seeds and because… Man, that would be easier than sprouting in
a way. [Jed]: Yes. 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
in 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 get their very nutty taste and they’re sort
of pleasant tasting. The problem is if you bake them, you kill
the enzyme, you kill myrosinase. Because it’s a… [Rhonda]: Right. So that’s something important, retention. [Jed]: 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. Excuse me. 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 would be pretty bitter. [Rhonda]: I’ll let you know, because I’m going
to try it. [Jed]: I thought you might. [Rhonda]: You made a pretty important point
for people and that is that the myrosinase enzyme is heat-sensitive and as you pointed
out, most people like to cook their cauliflower and broccoli or slightly steam it and their
trade-off for that is maybe it tastes a little better, but also it inactivates the myrosinase
enzyme. [Jed]: Correct. [Rhonda]: So they’re not actually getting
as much sulforaphane from the glucoraphanin as they would have 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 family? So, like, if you look at the broccoli sprouts
versus the mature broccoli or kale? [Jed]: So myrosinase appears to be about as
stable throughout the family. There are differences, subtle differences
to the protein composition of myrosinase. This is 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 make that conversion. And sometimes scientists think they’re so
darn smart. Just to back up just a little bit, we observed
that when you delivered 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 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. 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 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. [Rhonda]: Really? [Jed]: Really. It didn’t happen that way. What did happen is that we moved the bar up
so that instead of 10% bioavailability for 70%, we had about 35% or 40%. So the average moved up substantially. It was about 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, in 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. 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. [Rhonda]: 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? [Jed]: We have. We have. [Rhonda]: And you found that there’s only
a really small amount of supplements that actually contain what they say they contain? [Jed]: Yes. [Rhonda]: I think one of them you mentioned
was a French company that has actually sulforaphane in it, Prostaphane? [Jed]: Yes. So I’ve actually been told that there…and
I think it was someone in the industry that told me this, that there are something, like,
1,000 supplements that claim to have broccoli sprouts or broccoli extracts in them that
are on the market now. I certainly it would take me all of my waking
hours to try to vet that statement and validate the content of each of them. But, in our lab, we have looked at a number
of supplements. Some of those that are more prominent or that
you see advertised or some of those that we’ve been aware of because we know people that
have asked us about them. And many of them 20 years ago, there were
a bunch of supplements that said they have sulforaphane and sulforaphane cures cancer
because John Hopkins says so. This is highly inaccurate and they should
have been taken to court. But you can’t make statements like that. Nobody has shown that any of these supplements
prevent cancer or cure cancer. We certainly hope to be part of the group
of scientists who are able to put some teeth behind that evidence and, eventually, I think
one day it may be shown that in people, cancer can be prevented by taking something like
sulforaphane, but that has not been proven to date. So anyway, to get back to your question, we
have looked at a variety of supplements. Twenty years ago, when they started coming
out, there were many supplements that we could demonstrate were not even broccoli sprout
or broccoli. It had no broccoli in them yet they said they
were broccoli supplements. People were selling what they called broccoli
seeds and when you actually grew them out and grew plants from them, you grew cauliflower
or you grew canola or rapeseed from them or something else. Or in some more egregious cases, we found
stuff that was sold as broccoli seeds that was really alfalfa seeds. So a lot of liberties were taken, a lot of
shysters were on the market. I think that’s cleaned up somewhat now, but
now there are a ton, and as I say, I was told a 1,000, but many, many, many supplements
that say they have sulforaphane or glucoraphanin in them. We have analyzed a small number of them, those
that are made by labs or companies that we’ve read and heard good things about that haven’t
been challenged by the FDA for sanitation problems or for mislabeling. And there are supplements that contain glucoraphanin
alone, there are a few now that contain glucoraphanin plus myrosinase and there are a few that contain
sulforaphane. We are publishing this, should be out in the
next week or two, a paper in which we actually look at the bioavailability of sulforaphane
from a French supplement that is called Prostaphane. There’s been at least one publication that
looked at its ability to change the PSA trajectory in men who have had prostate cancer. [Rhonda]: And that’s a biomarker for prostate
cancer? [Jed]: It’s a biomarker for prostate cancer
return rate. And so those tablets, they’re tablets that
should be refrigerated to prolong the life of the sulforaphane in them. The bioavailability of the sulforaphane from
those tablets was essentially identical to that from powders that we made in the lab
by extracting broccoli sprouts and treating them with myrosinase and freeze-drying them. [Rhonda]: That’s very impressive. [Jed]: So we were delighted to see that they
worked. Yeah. Unfortunately, they’re not being sold in the
U.S. I hope that one of the supplement companies can… I hope that somehow or another business, the
business of supplements gets them to this country. I mean, we haven’t really talked much about
the clinical trials we’ve been involved with, but I can tell you that about a year and a
half ago, two years ago, we finally reached our limit in terms of the ability of our center
that’s called the Cullman Chemoprotection Center here at Johns Hopkins. We reached the limits of our ability to produce
broccoli sprout extracts for clinical trials, essentially, for other people’s clinical trials. We are a small group and we’ve done a number
of small clinical trials here, but we’ve had many, many people come to us looking for something
they can use in a clinical trial, people with expertise in areas different than ours like
asthma and allergy and COPD and a variety of psychological, neuropsychiatric conditions. And so we’ve supplied them with powders, freeze-dried
extracts that we made. I’d like to say we made them all at Johns
Hopkins. We actually had to go all the way across the
country to the largest freeze-drying factory in the world, it’s called Oregon Freeze Dry,
and do the extraction, hundreds and hundreds of gallons, do the extractions there and use
their massive freeze-drying facilities, then do all the quality assurance, and bring them
back to Baltimore. In many cases, we had them put into gel caps
so that they were easier to dose. And repeated quality assurance and microbial
testing and on and on and on. And then all of the paperwork and documentation
that goes along with that. I’m saying that, in a sense, to complain,
but to say that as a basic research operation, we were becoming overwhelmed with being a
little too helpful, I guess you could say, to people who had very interesting clinical
trials that we wanted to see happen. Because they were working with the stuff that
we had discovered and work with. So a couple of years ago, I went to a small
number of supplement companies and said, “Help,” and challenged them to take the supplements
that they were making that we had tested and verified contained what they said they had
and to offer to supply them for clinical trials that we were approached about partnering on. And not only to supply the material free of
charge, but to supply all the documentation and paperwork that would go along with an
application to an institutional review board or to the FDA, in fact, for an investigational
new drug application for permission to work on that disease with that compound. And a few companies did come forward. One of them was called Nutramax and they have
a product called Avmacol, which they sort of took a page from our playbook and they
made something with glucoraphanin and myrosinase. And so that’s actually been used in a number,
quite a large number of clinical trials now. And so I don’t think… We’ve tested it in people, of course. I don’t think there’s anything ready to be
published yet, but those publications will be coming along very shortly. [Rhonda]: And that actually does contain the
glucoraphanin and myrosinase and you’ve validated that? [Jed]: Yes, we would certainly not recommend
something to anybody without checking it. And we’ve checked every batch that they’ve
put on the market because we don’t want to be in a position… I don’t want to have egg on my face, and have
recommended to a friend that this is a product worth using and then have it turn out to be
a dud. [Rhonda]: So you mentioned the sulforaphane
one, which is the Prostaphane, the Avmacol, which has the glucoraphanin plus the myrosinase,
and then there’s the one that just has glucoraphanin. I think you mentioned it was by Thorne? [Jed]: They’re one of a number of companies
that have a decent…I shouldn’t say that have a decent one. They’re probably if you put this on a webinar,
there are probably going to be 10 companies that say, “We have a decent one, too.” I’m sure there are others, but we’ve tested… [Rhonda]: You’ve tested, and that’s important. [Jed]: Yes, we’ve tested a product by Thorne,
which is a medium or a large-size supplement maker, and their product is called Crucera-SGS. [Rhonda]: But that only has glucoraphanin
in it? [Jed]: Right. [Rhonda]: And this actually brings me back
to…I kinda want to get back to this and that is the microbiome. And so if you’re taking a supplement that
only has glucoraphanin and does not have the myrosinase enzyme there, then you’re relying
on what you possibly potentially have in a species of bacteria in the gut, which maybe
you can illuminate what that species of bacteria is, or if there’s ways we can increase it,
probiotics. Obviously, wiping out the gut bacteria. So people with chronic antibiotic use may
not be able to convert glucoraphanin very well, the sulforaphane, I would presume. [Jed]: Right. You must have read one of our papers. So in fact, we did show that, this was a number
of years ago now, we showed that if volunteers took a Fleet enema, self-administered enema,
which reduces the number of bacteria, certainly in their large intestine, by, I don’t know,
five or six orders of magnitude, and took a preoperative antibiotic course, in other
words, something that one would take prior to having intestinal surgery, they essentially
wiped out most of the bacteria in their intestines. And those people went from whatever their
level of conversion of glucoraphanin to sulforaphane and its metabolites was, which was, as you
heard earlier, was 10% to 70% to nothing. So they lost their ability to convert glucoraphanin
to sulforaphane. And then over the course of a couple of weeks,
I think, as I recall, we followed them, one or two subsequent challenges with glucoraphanin
two weeks and four weeks later, I think. They gradually regained their ability to do
that reaction. Clearly residual bacteria or new colonizers
in their guts had myrosinase activity. So we’ve looked at hundreds and hundreds of
people’s ability to do this conversion and nobody can’t do it. So everybody that’s living and breathing appears
to have myrosinase-producing bacteria in their gut. But as we said earlier, obviously, it’s at
very different levels. Just as clearly, although we don’t do bacterial
sequencing here, and this is a new and very exciting field of the microbiome, but it’s
very clear that there certain strains or certain species of bacteria that do have myrosinase
activity. Others have shown that there are, I believe
one of them is enterococcus, there are lactobacilli that have myrosinase activity. There are Bifidobacterium, I believe, that
have it. And again, this is not my field of expertise,
so I may have misspoken. But the bottom line is that there are a number
of species of bacteria that do this, but certainly not all bacteria in your gut. This whole, incredibly fascinating field of
the microbiome has certainly shown that each of us has different populations and different
ratios of different types of bacteria in our guts. And certainly, to the degree that this is
true, that’s going to affect the amount of myrosinase activity in our guts. I can tell you that we have done, we haven’t
published this, but we’ve done studies with mice in which we’ve challenged them with glucoraphanin
on a regular basis over time. And the goal was to try to push them by natural
selection, to try to push them to have more bacteria with more myrosinase activity. The fact that we haven’t published it means
we didn’t move the needle well enough or reproducibly enough to have a good story to tell, but certainly
that’s we believe might happen. Having said that, we look at real people and
we query them as to their habits. There is no evidence to date that people who
say they eat a pound of broccoli a day, that’s a little bit of an exaggeration, but people
who eat a lot of broccoli don’t necessary convert glucoraphanin better than people who
don’t eat much at all. So that speaks to some other selective pressure
on the gut on myrosinase-containing bacteria. [Rhonda]: Yeah. I would think that even just eating a healthy
meal in general when you’re eating a diet high in vegetables and fermentable fibers
and things that are growing Bifidobacteria and lactobacillus and all these species of
bacteria that are commensal bacteria, that even that itself would potentially then increase
your chances of being able to have more myrosinase because you’re having more of this commensal
microbiome, but I guess we don’t know. [Jed]: You know, we don’t know. I think both of our hunches are correct. But the proof is in the pudding. This whole issue of probiotics… [Rhonda]: Yes. That was going to be my next question. That would be interesting to view. [Jed]: Well, it’s fascinating. You know, in Europe, there is a lot, I think
the regulatory climate in Europe for probiotics is a bit more receptive than in the U.S. You probably know more about it than I do. But I know that the use of probiotics seems
to be increasing in the U.S., and studies by those who are expert in the field of probiotics
are mixed. [Rhonda]: Well, it’s the same case as the
glucoraphanin sulforaphane supplements. A lot of the probiotics in the market, there
is a lot of dead bacteria in them… [Jed]: A lot of garbage, yeah. [Rhonda]: …a lot of garbage. I mean, this is ubiquitous in all supplement. You know, I think there was even a study showing
something like 70% of, like, a lot of these supplements on the market are not actually
what they say they are, they don’t have the concentrations they say. But, yeah, I think that there is a lot of
mixed data and that comes down to not having quality probiotics and also the numbers. That’s another problem, too low numbers of…. [Jed]: Right, 10 billion per… [Rhonda]: Yeah, that’s nothing. You know, it’s like a drop in the pool. It’s not going to even move the needle. But there is a probiotic out there that I’ve
seen at least two dozen publications including clinical trials in humans and then there’s
more mechanistic studies in animals using VSL number three. It’s called, they’re sachets and they have
450 billion probiotics per sachet and they have a mixture of lactobacillus and Bifidobacterium
and some other ones but showing efficacy in treating IBS, Crohn’s. You know, so I think you can find quality
probiotics, but it’s just, again, it’s the same thing that you’ve seen in your field,
is finding the right one. [Jed]: Absolutely. I think the issue of the numbers of cells,
I mean, to a non-scientist consumer, “billions” sounds like a huge number. Well, yeah, it is, but it’s still…you know,
you can fit a billion bacteria on a pin, probably, well, maybe a teaspoon. Anyway, the issue there, though, is a lot
of the issue is survival. So if you boast about having billions of bacterial
cells of a certain type in yogurt, for example, and you’re not on proton pump inhibitors,
so you have an acid stomach and you send that yogurt through your stomach, how many of those
bacteria actually make it through the acid environment of the stomach? So, I mean, people have studied that certainly,
but there are studies, as you say, with a small number of specific strains showing effects. I think some of the more striking effects
have to do with childhood diarrhea and there are even studies showing effects on asthma. [Rhonda]: Effects on the brain. It’s incredible. [Jed]: Yeah. So I’m absolutely a believer that what’s goes
on in the gut matters to the rest of the body. There is no question about it. I think, as you say, a lot of the studies
suffer from the fact that what’s being given probably couldn’t have been expected to be
efficacious anyway because it just died or didn’t get there. But speaking of probiotics, wouldn’t it be
cool if someone came up with a myrosinase containing strain and put it in a probiotic
formulation so that you could take that along with your cruciferous vegetables? [Rhonda]: So cool. [Jed]: I believe that there are companies
that are working on that now because certainly, it’s well enough known what strains of bacteria
have myrosinase activity. There may be issues of getting that activity
maintained when you grow up vats full of bacteria to freeze-dry them, to put them in a formulation. But I hope it’s only a matter of time before
we see formulations that contain myrosinase and that are safe. I mean, obviously, safety of these probiotic
formulations is something that is a concern to the regulators and it should be. So we’ll see. I don’t think we’re quite there, but I hope
we are getting there. [Rhonda]: You actually shared something very
interesting about the effects of sulforaphane on a certain type of microbe species, H. pylori. [Jed]: So H. pylori, it’s full name is Helicobacter
pylori. Helicobacter pylori is a very interesting
organism in that it grows primarily or exclusively in the stomach. And it occupies that niche in a very unique
fashion. It apparently has an enzyme that is called
urease, but an enzyme that allows it to neutralize the PH in a little micro-environment around
the bacterial cells in the stomach. We shouldn’t use the term “gut” because we
also use the term “gut” to refer to the intestines. So the stomach is very acid, extremely acid,
that’s part of the way it does its job. And Helicobacter tunnels into the mucus layer
inside the stomach and, with enzymes, creates this little zone of neutral PH which allows
it to thrive, otherwise it would be killed as are any other, or almost any other bacteria
that enter the stomach. And it’s a very interesting critter, if I
can use the term. Can I call it “critter”? [Rhonda]: Yeah. [Jed]: It’s a very interesting critter because
some people, some very well-respected and well-known microbiologists, for example, Martin
Blaser at NYU, maintains and I happen to drink this Kool-Aid, I happen to believe this, that
Helicobacter has been around all during the evolution of humankind. Certainly, for tens of thousands of years,
people have had Helicobacter in their systems. And something like 55% of the world’s population
at the moment has Helicobacter in their systems. In some areas, recently in Japan and certainly
some areas in Africa and Asia, almost all people have Helicobacter, and some areas of
South America. And it’s a colonizer. It’s a commensal symbiotic organism, it would
appear. It may actually confer benefit on its host,
in other words, you, the person. If levels of Helicobacter get too high, if
the number of bacterial cells per square millimeter or per square inch or per square mile or however
you want to quantify them gets too great, then they start to have clearly pathological
effects. They can cause ulcers. They do cause ulcers and that can eventually
lead to stomach cancer. I believe the last estimate I saw was that
the World Health Organization considers Helicobacter to confer, I think, a three or four to six
fold increased risk of stomach cancer if you are colonized. But the question is if you are colonized with
Helicobacter, can you reduce the levels of colonization, keep it down to a low roar,
as it were. In other words, let a few of them hang around
in your stomach as long as they don’t overrun the system? And so the prescription for someone who has
Helicobacter in this country and I believe in Europe, I’m not a gastroenterologist, but,
is to wipe it out. So to treat it with so-called triple therapy,
three separate antibiotics and kill it so you can’t find it anymore. And I should say about 15% of people who are
given that treatment either can’t take it or it doesn’t work. So an alternative that many people find appealing
is a dietary approach to controlling Helicobacter. In other words, and we don’t have answers
to these questions, but if so many people around the world are colonized and it’s been
with us for so long and humankind is still humankind, are there perhaps benefits to having
it? So, for example, it’s been shown, I believe
this was Martin Blaser who showed this a number of years ago, that there is an inverse correlation
between Helicobacter infection and childhood asthma. So it may protect, due to stimulation of the
immune system, other mechanisms. It may protect against certain diseases, but
we just don’t know enough. So maybe reducing the levels of Helicobacter
in the stomach, again, keeping it to a low roar where it can’t cause or where it doesn’t
cause major inflammation, doesn’t give you ulcers may be enough to reduce the risk of
its causing stomach cancer at some point in the future. If it doesn’t cause inflammation and there
are only a few cells here and there that are sort of hanging on, maybe that’s okay. So that can be done by a dietary approach. And with that in mind, we actually looked
at the ability of sulforaphane to kill Helicobacter. Of course, if it had wiped out all the Helicobacter
in people who are infected, I would have been happy with that also. That would have certainly been an interesting
finding. What we ultimately found, and this was done
with collaborators in Japan in a 50-person trial, we found that Helicobacter can reduce
the levels…sorry, the sulforaphane or broccoli sprouts, actually, fresh broccoli sprouts
were able to reduce levels of colonization in infected people or colonized people and
were able to reduce markers of inflammation in those same people. That work grew from an observation that I
made with a different colleague, a French colleague who was visiting the U.S. on sabbatical,
Alain Lozniewski. So he and I discovered and published in about
2002 that in vitro, in a test tube, sulforaphane was very capable of killing Helicobacter. Not only did it kill natural strains, but
it killed strains that he had re-cultured from some of his patients. He’s a gastroenterologist, and it killed singly
and doubly antibiotic resistant strains. So, as you know, antibiotic resistance in
bacteria of all sorts in all settings is a huge problem and Helicobacter is no different. Once Helicobacter in people starts seeing
a bunch of antibiotics, some of them develop resistance including resistance to two of
the commonly used antibiotics that are used to treat it. So the fact that sulforaphane was equally
effective in killing them was, we thought, quite significant. And interestingly, sulforaphane is not as
potently antibiotic against a whole variety of other bacteria. [Rhonda]: So do you know why the H. pylori
is so sensitive to it? [Jed]: You know, we don’t. We thought we had some clues and, actually,
Dr. Lozniewski’s colleague in France had done some work on that which was never published. This colleague, for reasons that we need not
get into here, is no longer in the business of science and so that paper never got published
and we never really finished the proof. So we’re not sure why it’s so potently antibiotic. One thing I can tell you is that in the quest
for that answer, quite recently, Kitty Stephenson who works here with us and I started looking
at the ability of sulforaphane to inhibit urease, which is that enzyme that I told you
that neutralizes the PH in the mucus of the stomach. And we found that, indeed, sulforaphane is
quite an effective inhibitor of that enzyme. But, so again, we thought we had a really
eureka moment, but it turned out that wiping out that enzyme wasn’t sufficient to kill
Helicobacter because strains… How do I put this? Strains of Helicobacter that had been engineered
by others to not contain urease were still killed by sulforaphane. So it wasn’t…so the urease… So inhibiting urease might be important from
a disease prevention standpoint, but it’s not how the molecule killed the bacteria. Sorry to present such a complicated story,
but that’s the way things roll in this business. [Rhonda]: That’s science. Yeah, for sure. But the also very not surprising, to me, results
of it lowering inflammation is one of my obsessions with sulforaphane, generally speaking. I’m very interested in anything in my diet,
in my lifestyle that I can do that will lower the amount of systemic inflammation that I
have in my body. And it’s been shown, and you’ve shown this
and others have shown that even broccoli sprout extract powder given to people can lower C-reactive
protein levels by as much as 20%. Other inflammatory cytokines, IL-6, can be
lowered by something similar. You know, so it’s having a robust and measurable
effect in people that’s been repeatable in several different studies that I have seen. But one of the reasons I’m so interested in
this is because, well, inflammation really plays a role in a lot of diseases like cancer,
but it really seems to be a driver of the aging process. And I don’t know if you’ve…I think I mentioned
this to you briefly, but I actually think that sulforaphane may be a anti-aging compound. It’s one of the reasons I’m obsessed with
sprouting and taking it. I think that actually not only is it preventing
these diseases like cancer, but also may be actually delaying the aging process by activating
Nrf2, which then activates all these anti-inflammatory genes, activates the antioxidant genes including
all the glutathione-related enzymes. I don’t know if you’ve seen the study, but
I think I also mentioned to you that I would love to see some lifespan studies done in
animals. I know those are not easy to do. They take a long time. But there was a study that was done in this
red flower beetle. Have you seen this study? [Jed]: No, no. [Rhonda]: Okay. So let me tell you. So there’s a red flower beetle. Yes, it’s a bug, but they have an Nrf2 gene
that’s homologous to humans, also the FOXO gene, as well. So the scientists fed these red flower beetles
different doses of broccoli sprout extract and the doses ranged from, it was low to high,
I can’t recall, but it was a dose response. And what they found is that at, I think it
was at the highest dose, it extended the lifespan of these beetles by 15% and when they exposed
these beetles to a high oxidative stress all the time by keeping them in a warmer environment
constantly, it extended their lifespan by 30%. And it was totally dependent on Nrf2. So if they knocked down Nrf2, the lifespan
extension went away. So I was, like, this is a great teaser, right? Because if it’s happening and, I mean, obviously,
it’s a bug, but it’s the same gene, they have a homologous gene and if it’s extending this
lifespan of this critter that has the same, similar gene that we have, then I feel like
there is potential there. [Jed]: That’s fascinating. No, it wasn’t for me…so I have … [Rhonda]: I will send you the paper. [Jed]: Please. I have to ask you, is this a red beetle that
likes flowers or a beetle that likes red flowers? [Rhonda]: It eats red flowers. [Jed]: Okay. Okay. Well, that’s absolutely fascinating. Look, I can give you some anecdotes and tell
you of some false starts that we were involved with and I say “false starts” because since
they haven’t resulted in publications their work is not finished. But we have talked with colleagues at the
National Institute of Aging about, for example, looking at centenarians. There is a Baltimore centenarian project. So there are collections of people who have
made it to the ripe old age of 100 and more. Aren’t they a beautiful cohort to look at
the Nrf2-induced genes in? And I would be surprised if this hasn’t been
done already. We’ve talked about it for years, and I know
we’ve talked about doing it in animals. But doing precisely, as you suggest, here
is a cohort of very old people who are quite healthy. Do they have some… You know, everybody wants to know is there
something magic about that? But are the Nrf2-inducible cytoprotective
genes part of that equation? And we suspect that they might be. The prolonged lifespan experiments will pretty
much have to be done in mice. And again, there is someone at the…there’s
a colleague that I know we’ve talked to at the Institute of Aging who was interested
in doing that. I’m not sure if that ever happened. I had a high school student who wanted to
do a project here a number of years ago and we got her working on nematodes, Caernorhabditis,
which is a common experimental vehicle for those interested in looking at lifespan because
its lifespan is so short and it cycles quickly. [Rhonda]: I did a lot of work on C. elegans
when I was…before I went to grad school, lifespan studies. [Jed]: Well, we ought to get together and
do this experiment again if it hasn’t been done. You know, one of the problems with sulforaphane
research nowadays is I can’t keep up with it all. No one can really keep it up with it all because
there are two or three papers a week coming out on sulforaphane and quite a few more on
the Nrf2 pathway. I mean, if you try to be a renaissance person
and know all the literature in this field, it’s going to smoke you because there are
thousands, there are, I think, a couple of thousands of papers a year on Nrf2. So it’s very difficult to keep track of them
all and it’s possible that someone has done those lifespan experiments with C. elegans. Again, we started, we didn’t have much muscle
in it. We had a high school student who then had
to go back to this… [Rhonda]: Any preliminary data? I didn’t see anything in the literature, by
the way. I looked for C. elegans. I didn’t see anything with sulforaphane that
was published. [Jed]: No, we don’t have any preliminary data
from that student. We also had, I’m looking at my shelf for the
binder. It may not still be here. We had a colleague who was a bona fide expert
on C. elegans who was going to do some studies and I’m not sure if that ever happened or
if those were ever published. So, yeah, sorry, I wish I could jump up and
down with great… [Rhonda]: But do you agree with me here? I mean, just knowing what we know about how
sulforaphane is, as you mentioned, the most potent dietary, that we know of activator,
of the Nrf2 system, and knowing what we know, we do know that Nrf2 does play a role in delaying
aging, in brain aging, in tissue aging. It’s literally lowering inflammation and reducing
oxidative stress. These things cause aging. [Jed]: Right. So let me come back at you with a short story
about progeria, a disease of extreme aging or extremely accelerated aging and let me
also come back at you on the issue of brain inflammation, neuroinflammation, because there
is evidence in both of those cases and that actually does speak to the aging issue. I mean, I think we’d both like to see someone
do a study on centenarians or on C. elegans and just have a dramatic finding that lifespan
is extended. Maybe that’s coming. So the progeria study is that we got a very
small grant to look at a very terrible condition called progeria or Hutchinson-Gilford’s progeria
syndrome. This is a disease that is characterized by
accumulation of a protein called progeria, which is actually a mutant protein that has
a…again, I’m not sure if your audience is ready for this, but a farnesylation…a farnesyl
tag on it. [Rhonda]: Basically a marker that’s on top
of the… [Jed]: Yeah, sort of. So essentially, in a normal cell, you have
a cell membrane, you have some cellular architecture, you have a nucleus, and that nucleus holds
its structure, maintains its structure due to a number of reasons including the presence
of proteins called lamins. And these lamins form a network that helps
give it elasticity and shape and blah, blah, blah. And so one of the things that happens in the
pathway to making these lamins is you have a molecule, a sort of sticky molecule put
on the protein at one point and then taken back off at a later point. Why? I don’t know. That’s how cells do it. And so in progeria, actually, Francis Collins,
the head of the NIH made this discovery, I think, back in the early ’90s. There’s a mutation which allows this sticky
protein to persist and so that accumulates on the inside of the nucleus and it causes
a bunch of phenotypes, a bunch of symptoms which result in dramatically increased aging
so that kids who are born with it don’t live past their teens. It’s a uniformly fatal disease and it’s characterized
especially by cardiomyopathy, and stroke, and the diseases that many older people die
of. [Rhonda]: Happening in the teens? [Jed]: Happening in the teens. [Rhonda]: Right. So it’s definitely accelerated aging. [Jed]: Yeah. So very characteristic phenotype. The cells of those people are also characteristically
misshapen, the nuclei have all these problems with them, outcroppings and blebbings. They don’t look like nice sort of oval spheroid
nuclei. They’re misshapen. And so we’re studying cultured cells from
a progeria where control donors, tissue donors because there are only a few hundred kids
with progeria in the United States, period, and hundreds in the world. But anyway, it’s a terrible disease. We’re trying to help a little bit. Others have shown that sulforaphane has an
effect in reversing the phenotype in sulforaphane. Karima Gilali in Germany showed this a couple
of years ago. And we said that we were going to look at
a number of other isothiocyanates from different plants because sulforaphane, while it was
effective in reversing this phenotype, also was fairly…it was toxic at slightly higher
levels. So the therapeutic index or the window in
which you could operate and use it as a drug, let’s say, was very narrow. So what we’re doing is looking at other isothiocyanates,
very similar molecules, which we know also activate Nrf2 to see if there are some that
have much greater thresholds of therapeutic windows. [Rhonda]: And this is specifically in the
context of progeria [crosstalk 01:04:06]? [Jed]: Specifically, in the context of progeria. [Rhonda]: And that’s characteristic of any
sort of hormetic plant compounds, that there is a very small therapeutic window. [Jed]: Or not. I mean, there may be… Right. [Rhonda]: There’s a window. [Jed]: There’s a window, exactly. And we want to find windows that are large. So why do I mention progeria in terms of aging? Well, obviously, it’s a disease of acute aging
or accelerated aging. Many people seem to think that by understanding
a bit more about how we can reverse this phenotype in people with acute aging, that this may
also be applicable to normal aging and to perhaps slowing down normal aging. It turns out that all of us have some small
amount of progerin, this protein in our systems. And I believe the evidence is that it increases
somewhat as we age, not certainly to the acute levels that you find in kids with progeria. So we’re using sulforaphane to explore this. Since we got our grant, there’s a very interesting
and, I think, quite important publication from Tom Misteli’s group at the NIH showing
that, in fact, Nrf2 is very intimately related to this process in progeria. And that what happens is that progerin, the
sticky protein that I told you is on the inside of the nucleus, actually binds Nrf2 as it
enters the nucleus to do its signaling thing and it gloms it up against the inside of the
nucleus, so to speak, so that perhaps one among the chores of sulforaphane or among
the functions of sulforaphane are to increase the amount of Nrf2 that’s coming into the
nucleus, certainly, but it may also enhance clearance of mutant proteins and even progerin
from the nucleus. So there’s a huge amount that we don’t know
there, but it’s an exciting… [Rhonda]: Very exciting. [Jed]: It’s been exciting for us just studying
aging. [Rhonda]: Yeah. It sounds like even just the mutant progerin
would, seems like it’s stopping Nrf2 from being activated in that… [Jed]: It’s sort of holding it up at the gate. [Rhonda]: …essentially, it’s stopping it,
right. And so that’s possibly part of the pro-aging
effect, as well. I was reading somewhere, maybe you can confirm
this, that sulforaphane does increase the activity of Nrf2, like, Nrf2, I think it’s
something like 60%. Like, Nrf2 is activated every 180 minutes
or something like that. And sulforaphane bumps that up a 60% increase
in it being activated. So I don’t know if that’s… [Jed]: Yeah, I can’t comment on that. Sorry. But I mean… [Rhonda]: But it’s activating it more often
for sure? [Jed]: Correct, correct. Yeah. [Rhonda]: And that’s, for me, what I want. Another quick question I wanted to ask you… [Jed]: It up-regulates its production. So if you look at RNA levels for Nrf2 or for
Keap1, it’s tether protein that’s present in the cytoplasm. After treatment with sulforaphane, you see
those levels going up. So 60%… [Rhonda]: I think that was a translocation
of the nucleus. That was the increase that it was doing. [Jed]: Okay, yeah. Unfortunately, I can’t comment on that, just
don’t know. [Rhonda]: Yeah, I mean, that’s okay. I’ll talk about it at another… [Jed]: But I’m sure it’s true, I believe you. [Rhonda]: Well, it was from a publication. So if the publication was accurate. But so we’re talking about aging and also
brain inflammation and, I mean, obviously, there’s been some interesting studies on sulforaphane
in the brain. [Jed]: Yeah. So this is an area where we’re actually spending
a lot of our time now, is partnering on clinical trials that are looking at just that. So it turns out that the neurologists and
those who have been studying the brain and diseases of the brain for a long time in,
I guess, the fairly recent past have determined that inflammation is a huge component of a
number of those conditions. Schizophrenia, autism, Alzheimer’s are among
them. And so we can we can speculate as to how that
inflammation has an effect. As far as I’m aware, you don’t see increases
in brain volume. It’s not that kind of inflammation, but markers
of inflammation clearly are up in people with these conditions and can be reversed in some
cases with anti-inflammatory drugs. And so
people have come to us recently with the question, “Okay, we know sulforaphane reduces inflammation. You know, can it possibly help with autism,
Alzheimer’s and schizophrenia?” The three that we’re actually looking at. I should back up, though, and say that sulforaphane,
and isothiocyanates like it, have many effects. They do affect many pathways. We talked about Nrf2. I may have made it seem like that was the
best thing since sliced bread, and the only thing. It’s not the only thing. We also mentioned antibiosis, selective antibiosis
against Helicobacter. What we haven’t talked about yet is the fact
that sulforaphane actually inhibits the NF-kappaB pathway, which is one of the main inflammatory
pathways in the body. And there’s even some, as it’s called, crosstalk
between the Nrf2 pathway and the NF-kappaB pathway, so the inflammatory and cytoprotective
pathway. Sulforaphane also, sorry, up-regulates 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 lab or came to our attention. So Dr. Andy Zimmerman, a colleague at…who
was at the time at Harvard Medical School and the Mass General Hospital came to Paul
Talalay back, I don’t know exactly when, 2008 or 2009 or 2010 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’re 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 up-regulating 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 rela-,…” [Rhonda]: Improve. [Jed]: “They improve and that’s likely related
to this heat shock response. Wouldn’t it be interesting if sulforaphane
has an effect?” 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. You know, more effective clearance of oxidative,
reactive oxygen and reactive nitrogen species. [Rhonda]: Right. I never thought about heat shock protein playing
a role in autism. That’s very interesting. I mean, neurodegenerative diseases for sure,
but I didn’t… And so that’s an interesting connection he
was making that I wouldn’t have made, but I can see how he is making it. It’s very interesting. [Jed]: Yes. So the paper is 2007, Curran, C-U-R-R-A-N,
is the first author. We’ll get you a copy. So yeah, it’s a fascinating potential connection. And so that was sort of…that was what got
the collaboration started. So we supplied broccoli sprout extract, and
they, up in Boston, looked at, I guess it was about 44 subjects, all men, all young
men, boys, men. As you probably know, autism is about four
to one, male to female in terms of its incidence in this country, anyway. And less than or more than 1 in 100 kids now
are born with autism. So it’s a huge problem. I don’t need to go into detail about why it’s
such a big problem, but, because you’re an expert on autism among other things. [Rhonda]: Not really. [Jed]: But, well, you’ve studied it. So at any rate, we did this trial. It was published in 2014. We, for various reasons, biomarkers of inflammation
of the Nrf2 pathway and heat shock response were not evaluated in blood from those subjects. But what we showed was a rather dramatic reduction
in many of the symptoms of autism in about half of the subjects compared to placebos. Those who were given placebo instead of broccoli
sprout extract in which there was no detectable change. [Rhonda]: I think it was, like, a 37% improvement
in, if I remember correctly from your paper. Yeah, it was very, very robust from a small
amount. [Jed]: It was dramatic. Right, the n was small, the number of subjects
was small, but it was a dramatic improvement. I am so sad that we never got the biomarker
data from those subjects, although theoretically, it’s still available. As a result of that trial, a lot of people
got interested in the possibilities. And so Dr. Zimmerman and his team, including
the Cullman Chemoprotection Center here, have a follow-up grant from the Department of Defense
to study a younger cohort, male and female, boys and girls, about 50 subjects. But a similar trial design and it is going
to be…it is biomarker-rich. So we’ve already done a pilot study with 10
subjects in which we evaluated… We refined our ability to collect samples
and to process the biomarker samples. We’re collecting blood from all of them. And this is a trial design where, half of
them, half of the subjects are getting, actually, Avmacol, one of the supplements, the dietary
supplements, the one with glucoraphanin and myrosinase, half of them are getting that,
half of them are getting a placebo for, I think, it’s 15 weeks, for about the same amount
of time as we gave subjects in the previous trial. Biomarker-rich, then there’s a washout period,
and then everybody goes on the sulforaphane product, the Avmacol, for another 15 weeks. Dr. Hua Liu and I…she’s doing most of the
biomarker work here at Hopkins. She and I were just up in Worcester, Massachusetts. The team is now at UMass Medical Center in
Worcester, Massachusetts. They’ve processed about a third of the subjects. So we’re about a third of the way through
completing the trial. And we’re very excited, obviously, about what
we may find and about getting to the task of processing these biomarkers. [Rhonda]: Very exciting. And what was the dose difference from the
first trial? The first trial, the dose of… [Jed]: Well, it’s a little complicated, but
if you bear with me, the first trial delivered sulforaphane-rich broccoli sprout extract. [Rhonda]: Okay. [Jed]: Okay. Remember that’s 70% bioavailable, okay. This trial’s delivering glucoraphanin plus
myrosinase. It’s calibrated to deliver about the same
amount as the previous trial. So between 100 and 150 micromoles per subject
per day. [Rhonda]: Is there a reason why you’re not
doing a dose response or trying higher doses, as well, to see if there’s a more robust effect? [Jed]: The next trial will do that. [Rhonda]: Okay, so that’s in the pipeline? [Jed]: Well, it’s in this pipeline. [Rhonda]: Okay. [Jed]: Yeah. So, I mean, look, after a trial like this,
especially one where we were not able to publish biomarker results, there are many people saying,
“Wow, that’s really interesting, but it’s got to be repeated.” So we and others are trying to repeat it just
essentially as closely as possible to the way it was designed. You know, it does make sense and it’s unfortunate. If these trials weren’t so damned expensive,
I mean, we could try all… [Rhonda]: It’s expensive and long to do. [Jed]: We could try all conditions. [Rhonda]: I know, I imagine. It’s very, very exciting. [Jed]: It’s exciting, but it’s very expensive,
its labor-intensive, and it also…you know, you’ve got the hopes, and fears, and desires,
and tears of a lot of people involved. These are conditions that that hurt to see
people going through. And so to do a whole bunch of trials with
a whole bunch of conditions might also make the people who are suffering from these conditions
really think that this is…that we already have the answer. This is why I’m so afraid of some of the cancer
prevention trials that are being done. You know, people get on their high horse and
they don’t know what they’re talking about. You know, again, one of the most frequently
heard things, for me, is, “Oh, scientists at Johns Hopkins say this cures cancer.” I mean, I’ve heard that said about so many
things, not just, certainly not just our work. It ain’t true. 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 other, additional
autism trials using all using Avmacol, and this is 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… [Rhonda]: I mean, this is something that’s
available for people right now. [Jed]: It’s available, and we know that it
produces sulforaphane and we know that it’s a decent product and it has been through all
sorts of quality assurance. But so 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 any more.” 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 up-regulated or not and
hope to be able to make some correlations with symptom reduction and biochemistry. There is a trial just starting at the University
of North Carolina, there’s a trial at Rutgers. 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 to study drug or
supplement is they’re…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, 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. [Rhonda]: 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 it 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 not that, 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. [Jed]: Very possible, yeah, yeah. You know, this is another case of studies
that didn’t happen. There were grand plans for a large multicenter
study in Europe looking at the effects of sulforaphane on autism. PI was in Spain, highly regarded, the study
didn’t get funded and it didn’t happen. [Rhonda]: Autism or Alzheimer’s disease? [Jed]: Sorry, Alzheimer’s, Alzheimer’s, yeah. I mentioned schizophrenia, in terms of schizophrenia,
we now have two studies that are just starting. Again, they’ve all been approved. They’ve been through FDA approval and institutional
approval, one in Baltimore at the Sheppard Pratt Hospital, which is a psychiatric hospital
in Baltimore, and the other in China. Again, the idea is to look at remission or
reduction of symptoms of the diseases of schizophrenia and look at a variety of biomarkers in blood
and perhaps, urine. [Rhonda]: Were you involved in that pilot
trial that was published in… There was a small trial in schizophrenic people. [Jed]: This was the [inaudible 01:25:56]? [Rhonda]: Yes. Yeah. [Jed]: No, I know about it and I’ve… [Rhonda]: So is this based off of that or
is this sort of where…? No? [Jed]: No. So they only had 10 subjects in that trial. This was Dr. Hashimoto’s work, I think he
was the corresponding author on that. I’ve talked with him, familiar with the work. So, I mean, based on publication precedent
or history, I guess, you could say we’re following off his work. But the way this actually evolved, I think,
is that the principal investigators saw the autism work and heard us talking about anti-inflammatory
responses in heat shock effects and so on and became interested in doing the trial. Certainly, they and others in the schizophrenia
community are familiar with the paper you’re talking about. And there’s also some very interesting animal
modeling in schizophrenia, some from the same group. So, yeah, I mean, I think all signposts are
pointing in the direction… [Rhonda]: That’s cool. There’s definitely a common denominator with
oxidative stress and inflammation in both autism and schizophrenia, but also in depression. And this is another brain dysfunction, I guess,
if you want to call it that, but inflammation has been shown now to play, actually, a major
causal role in depression. And there’s been some animals studies that
you may have seen where the sulforaphane, broccoli sprout extract in sulforaphane has
shown to be even as good as fluoxetine, which is Prozac, in alleviating, like, all these
different methods of stress they have to make an animal depressed, and then they give it
Prozac or broccoli sprout extract and it works just as well, which is extremely interesting. [Jed]: I totally agree. We won’t talk about the way those experiments
are done here because I think they can be sort of… [Rhonda]: Inhumane? Some of them? Some of them. [Jed]: They’re distressing to hear about,
yeah. But needless to say, it’s better to do them
on mice than on people. Yes. In fact, just last week, I was at the Stanley
Medical Research Institute, its annual meeting in Baltimore and there was a lot of talk about
inflammation and depression. They’re focusing on bipolar disorder and schizophrenia. And in fact, they funded the study at Sheppard
Pratt that’s just starting, as I say. So, yeah, I mean, there is so many conditions
that we hope may respond even if only partially, and the fact that it can be a dietary approach
is, I think… [Rhonda]: Wouldn’t that be cool? [Jed]: That would be… [Rhonda]: I mean, if people could, instead
of getting on something with side effects possibly takes broccoli sprouts or some sort
of broccoli sprout extract or supplement that’s out there that’s really effective, that would
be so…because it’s just, it’s so good for you. The sulforaphane, the broccoli sprouts are
so good for you. So I just would be really excited to see that
happen. [Jed]: Well, you’ve reminded me that I need
to give a little lecture about supplements versus food and the lecture, I guess, goes
sort of like this. In this country, a lot of people take supplements,
right? A lot of people eat Big Macs and don’t exercise,
and there’s nothing…there seems to be very little that those of us who call ourselves
nutritionists or nutritional biochemists or health communicators or whatever we call ourselves,
there’s very little we can do to reverse that. Some people are making some progress and that’s
good, but when I came here 23 years ago, I thought part of my job was to get people to
eat healthier diets, diets rich in fruit and vegetables. I still think that’s my job, part of my job,
but I see how well it works, and a lot of times, it just doesn’t work. And so there’re many people who are going
to watch this webinar I’m sure like to think that they’re going to eat a healthier diet
and adopt a healthier lifestyle, but may not do it. And a lot of those people probably are going
to wind up looking for supplements, and if they see a broccoli sprout supplement and
hear us talking about, it’s likely they’ll buy, they’ll buy one and they’ll take that
and continue to sit on the couch and watch TV and eat French fries. I mean, let’s keep fighting it, but I’m not
sure how successful we’ll be in the long run, but now, so let’s move this lecture to another
part of the world. Let’s move the lecture to the so-called developing
world, a term I don’t like because it implies that we’re developed and I don’t think we
are especially after what just happened in November in this country, but we won’t talk
about politics. So you go to the developing world where people
can barely afford live on a couple of dollars a day, can’t afford a course of antibiotics
to treat, for example, Helicobacter infection, where diseases are…sorry, conditions like
autism may be a death sentence, blindness in children may be a death sentence because
if they can’t see, they may run out in front of a car or a bicycle or fall in a lake. I mean, the tragedies that befall people without
a so-called developing world social structure to catch them are legion. But as long as those people are still eating,
the possibility that we can, by suggesting a single alternative plan, for example, that
they may be able to have an effect on autism or Helicobacter colonization or the risk of
various cancers, for example, or asthma, or air pollution injury. I think there’s a very real possibility that
we can make a difference. I mean, when you talk about things like cancer
prevention, if I invent a magic potion, I’m not going to see the results of it in my lifetime
because people are going to have to be taking it for 10s, and 20s and 30s of years before
the effect is manifest epidemiologically. And those trials are far too expensive to
do as an intervention when you’re looking at a population and asking “Does this prevent
cancer in someone who’s not at high risk for that particular cancer?” Anyway, I’m digressing. Go back to the developing world. So if you can get someone to change one of
their foods or change a few of their foods, or grow something different, then I think
the potential to have a real effect is quite impressive. We’ve worked the numbers, we’ve published
a few times on, so the cost of prevention, and when you compare the cost of a dietary
change, even in this country, to the cost of some things like automobile seat belts
and statins and a variety of other preventive approaches, a dietary change is way down on
the list in terms of cost. Take that to the developing world, I think
it’s even a more impressive bang for your buck. And I say that because we’re talking about
broccoli sprouts and we’ve been talking a lot about supplements. When you go to the tropics, which is where
most of the developing world is, there are plants, and I think I mentioned moringa earlier. Moringa, it happens to be a tropical tree
that grows everywhere. It’s a weed, and it’s also full of an isothiocyanate
that is, in many cases, more active than…it may be better than sulforaphane in many situations. Better or worse, but it’s sort of on the same
level of efficacy of sulforaphane. I’m mentioning that because we’ve studied
it here and I’ve been involved with actually trying to promote moringa for nutritional
reasons. And I’ve been very fascinated by the potential
pharmaceutical or pharmacologic potential of moringa. But it’s but one example and there are others
that will cite you various other examples of plants that can grow in developing areas
of the world, can grow in the dryland tropics, or the wet rainforest tropical regions that
could, theoretically, really be game changers not only nutritionally, but in terms of disease
prevention in those populations. And I think we really need to spend, I guess,
the preaching part of this, I think we all need to spend more time, and attention, and
money on some of those plants. And they may actually have benefit for those
of us in the West anyway. I mean, I’m not suggesting that we would want
to bring tropical moringa here and try to get people all over the U.S. to eat it because
it’s got various pharmacologic value to it nor am I suggesting…I certainly wouldn’t
suggest that we try to cover the world, the equatorial world, with broccoli sprouts because
they just won’t work. Broccoli is a temperate climate plant and
it’s too…you know, sprouts are too fragile to import to the tropics or export to the
tropics, I think. But the point is that there are plants in
various regions of the world that could be adopted, or engineered, or taken over and
we should really explore them a bit more, I think. [Rhonda]: So I have a couple of questions. So the moringa, does it activate some of the
same pathways, different pathways that sulforaphane does? [Jed]: It does… [Rhonda]: There’s a lot of crosstalk… It does? [Jed]: Yeah, yeah. So the isothiocyanates have this N double-bond,
C double-bond S-group. Again, non-chemists won’t care, but that’s
the active part of the molecule that is responsible for most of its activity, we think. The other part of the molecule that’s hanging
off that is responsible for solubility and permeability, and contributes to its biological
activity. I think it’s not as relevant in terms of the
activity of the molecule. And so all of the isothiocyanates from cruciferous
plants and from moringa all have that NCS group, which is what’s responsible for binding
to the Keap1 molecule. There are two sulfhydryl groups on reactive
cysteines on that Keap1 molecule, and our colleague Dinkova-Kostova has shown that. And the isothiocyanate binds there and causes
a change in conformation of that protein. So if you have a different isothiocyanate
that maybe is bulkier, maybe it’s less effective in getting in that position on the molecule,
but, yeah. [Rhonda]: Okay. And can we cultivate moringa in places in
the United States? [Jed]: We can, and it’s being cultivated in
southernmost Florida and I think even in Southern Arizona and Southern California. It doesn’t tolerate frost. So you have to protect it from frost, but,
I mean, it’s like oranges and lemons and citrus fruit in that respect. So it can be grown in the States. And there are people…I’m actually on the
scientific advisory board of a company that’s producing moringa in Ghana in Africa. They produce in women’s cooperatives and they
produce in a responsible way, and they are very attentive to cleanliness of the product
that’s coming back and they have something that they sell in the U.S. They put it in bars, and they put it in drinks,
and they sell the powder plain. There a number of companies that do that. [Rhonda]: I’ve seen it at Whole Foods. [Jed]: Yeah, yeah. [Rhonda]: Moringa, yeah. [Jed]: Yeah, I think in fact… [Rhonda]: It was in health food stores. [Jed]: Yeah, yeah. There are also some really lousy companies
that are producing moringa. There’s a multilevel marketing company that’s
producing it and making outlandish claims. So as with dietary supplements… [Rhonda]: Do you have like a list of…do
you know which ones are more reliable based on… [Jed]: Well, the company that I’m fond of
is called Kuli Kuli. [Rhonda]: Kuli Kuli? [Jed]: K-U-L-I K-U-L-I, yeah. And I think that… [Rhonda]: And they make in the United States
or they have… [Jed]: No, they produce it outside of the
United States. They bring it in. [Rhonda]: Oh, they are importing, okay. [Jed]: Yeah, there probably are companies
that are producing it in the U.S. I’m sure there are. As with nutritional supplements, you have
to be very careful of claims that are made and what’s really in it. So there’s a company, I think the biggest
company that’s been identified with moringa. I’m blanking on the name of the company, but
they made a drink and they’re a multilevel marketing company and they made many, many
irresponsible claims. They invoked the name of Johns Hopkins even
in some of their advertising and frankly, I hope they’re not doing well. So you just, you have to be careful. [Rhonda]: Okay. 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 in more developed nations and how it can be very powerful in cheap dietary
intervention that may make a huge difference in people’s health in those nations. It just came to my mind knowing what I know
about sulforaphane and how sulforaphane is very powerful, and this has been shown in
multiple clinical studies, to immediately start to detoxify air pollutants that were
exposed to, like, benzene, alkaline, but benzene is a big one. Like, I mean, you start to excrete benzene
by, like, 60% after just 24 hours of taking broccoli sprout extract. And I’m thinking about developing countries,
there’s been a few studies coming out recently that the air pollution and some of these things
are a big problem over there, and it’s been shown to cause very high stroke risk in young
people even because these things are inflaming the blood vessels. It’s not just benzene, it’s particulate matter
and things like that, as well. But still, what’s very interesting, if moringa
would also be activating these phase II detoxification enzymes, which would be getting rid of some
of this compounds and even playing a powerful role in just reducing inflammation in the
body and preventing people from having strokes at such young age. So you’re right. I think it is very important. You know, people here in the U.S., there’s
a very large population of people that are interested in aging well and not degenerating
and I’m part of that group. [Jed]: We all are. [Rhonda]: But there is also people that have
serious risks that are living in countries where they don’t have the luxury of going
to a health food store and eating kale smoothies and things like that. [Jed]: Exactly, exactly. [Rhonda]: So that’s really cool that you’re
involved in that research and advocating for that, as well. Dr. Patrick: Well, I think, I actually got
involved with a not-for-profit back in the early 2000s that was advocating the use of
moringa from a nutritional perspective and I’ve sort of stayed in touch with that group
ever since. And there was a lot of effort to try to get
some clinical trials based on its nutritional benefits. It’s very high, the leaves are very high in
protein, way higher than kale, or broccoli, or most other leafy green vegetables. [Rhonda]: Yeah, that’s interesting. [Jed]: Yeah. And it’s also the leaves stay on the trees
longer than just about anything else in cases of drought. But there was not the uptake to do a clinical
trial, and now there is so much sort of dogmatic promotion of moringa for its nutritional value
in those areas of the world that it’s so widely used now that I think it’s going to be difficult
to get some of the rigorous Western-style clinical trials done that we might desire
because everybody is just assuming that it’s nutritionally, it’s a panacea. [Rhonda]: And where is it being used mostly? [Jed]: Really, all over the tropics, certainly
in the Philippines, in large swaths of West Africa and South Africa and in India. I mean, its origin was in northern India near
the Pakistan border and it spread around the world since. It spread a long time ago, but it spread around
the world from those points of origin all over. [Rhonda]: Do people just eat the leaf? Like, how are they preparing? What are they doing? Do they make moringa smoothies? [Jed]: Well, some people do. It’s interesting, but moringa, because it’s
sort of a ratty-looking tree, I mean, it’s a 20, 30, 40-foot tall tree, but it’s sought
of ratty-looking and it’s sort of hardscrabble. Yeah, it’s not gorgeous and the leaves… It was called the horseradish tree or the
drumstick tree. Drumstick tree because it has long seed pods
that look like drumsticks. Horseradish because it’s stringent. [Rhonda]: Does it taste like horseradish? [Jed]: Yeah, it’s harsh. It’s sort of like eating Japanese radish,
daikon. So, because…and I can give you some to try
if you’d like later. [Rhonda]: I would, actually. Love to try it. [Jed]: Okay, yeah. Because of that harsh taste… Actually, I have some on my shelf right over
there. Because of that harsh taste and because of
the way it sort of grows like a weed, it’s regarded in a lot of areas as a famine food. And it has also been sort of a last resort
in cases where people are starving. And from what I understand from my social
and behavioral science colleagues, many times, plants like that sort of get a stigma attached
to them. So people with little excess money, people
who are doing okay may reject what are thought of as famine foods as sort of low class when
they don’t need them. So getting people to voluntarily adopt a food
like that may be difficult and has proven to be difficult in some areas, and apparently
that’s one of the reasons. However, it’s quite widely eaten, the dried
powdered leaves are very easy to store so they maintain their high protein content for
a long period of time. That is not the case with things like spinach
and kale and some other green leafy vegetables. I mean, imagine drying iceberg lettuce leaves
and powdering them and then having them later, yuck. So in the tropics, dried powdered moringa
leaves are found in a lot of areas and are used in food. It’s funny, the “Hopkins Magazine” just did
a little profile on our involvement with moringa and they quoted me as talking about the first
time I had cooked moringa in Africa, which was in Ghana at an international moringa meeting
and it was moringa leaves… So I’d had them powdered and I’d had the supplements
made from them back in the U.S. But this was in 2006, I think. There was a stew and it looked sort of like
saag, like Indian saag, like spinach stew, had some chunks in it. And I was offered some at this meeting on
the shores of the Atlantic, a beautiful scenery under sort of tiki huts. And I ate it and then I asked my hosts what
the chunks were and it was rat. So I was a little grossed out by my first
sampling of moringa made as it’s eaten locally, but I actually… [Rhonda]: Tastes like chicken? [Jed]: Tastes like chicken? Yeah, exactly. Exactly. [Rhonda]: Wow, I don’t know if I could stomach
that, especially after experimenting on rats. So these leaves are high probably in also
other micronutrients, folate, magnesium. [Jed]: They are. They are. [Rhonda]: You know, but what’s the glucosinolate
that is stored in the moringa, what is it called? [Jed]: It’s called glucomoringin. [Rhonda]: Glucomoringin? [crosstalk 01:48:11] I have to remember. [Jed]: Yes, the lengthy scientific term is
4-L-alpha-rhamnosyloxypyranosyl-benzyl glucosinolate, so there. [Rhonda]: Wow. I’ll go with Glucomoringin. [Jed]: So, you probably prefer the shortcut,
yeah. [Rhonda]: And what’s the active… Oh, that’s the isothiocyanate? [Jed]: That is the glucosinolate and it’s
hydrolyzed by myrosinase that’s present in moringa leaves to moringin, or for 4-L-alpha-glucopyranosyloxy
benzyl isothiocyanate. So it’s got a big, honking sugar group, a
rhamnose sugar group, and a benzyl group attached to this NCS. [Rhonda]: Okay. [Jed]: So it’s actually, structurally, it’s
very different because it’s got a lot of excess chemical baggage. So in terms of steric hindrance getting to
a protein, getting to a molecular site, it’s quite different. But as I said before, it’s actually more active
in some assays and less in others. [Rhonda]: And so forth. [Jed]: And so forth. [Rhonda]: It’s very interesting and it kind
of brings me to just another quick question because you mentioned daikon and that’s something
that I’ve seen in several studies where there seems to be some particularly stable form
of myrosinase in daikon. Is that true? [Jed]: Yeah. [Rhonda]: You know where I’m going with this? Can you eat daikon or add some… Is it found in mustard powder? Is that… [Jed]: It is. It is. [Rhonda]: Okay. Can you sprinkle mustard powder on your broccoli
and increase the bioavailability? That’s what I was getting at. [Jed]: I think so. And so where you’re, I think you’re trying
to draw me out on the issue of myrosinase and where it is, and how it is, and what the
complications are. So myrosinase is a simple enzyme. It’s a protein. It turns out that there are companion proteins
that have slightly different activities or that modify the products of myrosinase. To make a complicated story even more complicated,
the glucosinolate gets converted by myrosinase, not directly to an isothiocyanate, but to
an unstable intermediate that then rearranges and forms the isothiocyanate. So there’s an opportunity for other enzymes
to come in and sort of re-direct the pathway. And one of those enzymes is actually present
in broccoli and at normal physiologic gut PH, temperature and without an excess of iron,
ions and so on and so forth. There’s not a lot of diversion from isothiocyanate
to these other compounds, but most of the other compounds are not necessarily bad for
you, but they don’t have the same phase II enzyme-inducing activity so you’re essentially
wasting or losing some of the precursor. [Rhonda]: Are we talking about sulforaphane
nitriles? [Jed]: Sulforaphane nitriles… [Rhonda]: So they’re not bad. They’re just not… [Jed]: They’re not effective, right. [Rhonda]: Okay, because that was another question
I had. [Jed]: Well, there are some other compounds
called indoles that we can talk about in a minute and they’re present in the broccoli
heads. They’re not present to any large degree in
broccoli sprouts. So indoles from broccoli form, we’re going
all over the map here, but I’ll come back. I’ll come back. So indoles from broccoli form something called
indole-3-carbinol or I3C, which is omnipresent in health food stores or supplement sites,
or DIM, D-I-M, diindolylmethane. These compounds have gotten sort of a mixed
review from a health perspective because it’s been shown they can polymerize or form dimers
or tetramers that actually resemble dioxin, the potent toxin. And so in animal studies, now I haven’t updated
my brain on this for a number of years, but when I last did about four, five years ago,
there were an equivalent number of animal studies showing a cancer-preventive effect
of indole carbinol, I3C, to those which showed that it actually promoted cancer. And some of these were even in the same animal
model and what it turned out was that the preventive effect depended on whether you
gave I3C before or after you gave a carcinogen. So as a lab animal, you’re in a cage, you
eat what you’re given, and then the way these experiments are done is a carcinogen is administered
usually for once or for maybe three or four days either before giving the protective compound
or after giving the protective compound. And then you follow that animal out or those
animals out for many, many weeks until cancers develop and you count tumors, and you determine
that there was protection or not. It depended on when vis-à-vis the carcinogen,
they got the protection. That’s great for an animal…well, it’s not
so great for the animal, but it’s great for an animal experiment, but you and I get our
carcinogens continuously, one might imagine, right? Whether it’s from sunlight or aflatoxins in
our food… [Rhonda]: Or benzene. [Jed]: …or benzene, yeah. So we get our carcinogens continuously and
we do get to choose when we eat our protective compounds if you want to look at it that way,
I suppose, or else, we’re eating our protective compounds all along if we are eating a protective
diet. I think I’m going to be able to get back to
what you originally asked me, but we were quite happy when we determined that in broccoli
sprouts, there were essentially no indole glucosinolates, therefore, there was no indole-3-carbinol
or diindolylmethane that we would have to worry about. We wouldn’t have to do this sort of mental
arithmetic and think “It’s unbalanced, is this a good thing or not?” Now, the epidemiologic studies still say that
eating more broccoli or more cruciferous vegetables is good for you from the perspective of a
bunch of different cancers, etc., etc. [Rhonda]: Across the board. [Jed]: Across the board, yeah. So I don’t think that I3C, indole-3-carbinol,
is bad for you. A lot of women take it for menopausal problems,
it’s invoked in the estrogen cycle, and I can’t remember off the top of my head exactly
what the indication is, but I don’t think it’s bad for you. We don’t worry about it with broccoli sprouts
because it’s just not a factor. So back to your…we got off track, but you
asked about myrosinase. So all the cruciferous vegetables do have
myrosinase. Many of them have these other accessory proteins
or additional enzymes that will direct the conversion of glucosinolates not just to isothiocyanates,
but to some other stuff. And, interestingly, daikon or Japanese radish
doesn’t have… I’m not sure that I can say it doesn’t have
all of them, but it doesn’t have the main enzymes, epithiospecifier proteins, they’re
called, that do some of this redirection to alternative products. So, in fact, if you were to eat cooked broccoli,
so just, let’s get hypothetical now in the kitchen. So if you were to eat cooked broccoli and
you were to want to get as much of a sulforaphane benefit as you could from it, you might add
grated daikon or ground up daikon seeds even at very low level to facilitate the conversion. In other words, add live enzyme to facilitate
the conversion and you wouldn’t have the complication of that other enzyme. Actually, this has been published. My colleague Yuesheng Zhang who was one of
the people who discovered sulforaphane originally, he was the one who actually pointed this out
to us many, many years ago and it was subsequently published by others in Illinois. But the fact that broccoli has this epithiospecifier
protein means that you’re not getting complete conversion to sulforaphane if you use the
broccoli enzyme. So for reasons that had nothing to do with
knowledge of that fact when we first started making broccoli sprout extracts rich in sulforaphane,
I was adding in a very small amount of seven-day-old daikon sprouts to the boiling kettles once
they cooled down to catalyze the conversion. And the reason I was doing it is because once
we boiled broccoli, we kill the native enzyme, and I wanted to add something that had the
biggest bang for its buck of myrosinase and I had found that daikon sprouts had a hell
of a lot of myrosinase activity. It was really just sort of a greedy…well,
I was actually doing it because I wanted as little contamination of the taste and the
other compounds present in daikon sprouts. So I was able to add 1% or 2% by weight daikon
sprouts to the broccoli mix to get complete conversion. And as I say, Yuesheng Zhang, who’s now at
the Roswell Park Cancer Institute, then pointed out to me that, “Hey, did you know that we
found the epithiospecifier protein isn’t in daikon sprouts?” So, anyway, a long story, but… [Rhonda]: So that’s really a useful little
hack for people including myself. [Jed]: Yeah. But daikon sprouts are pretty harsh-tasting. I mean, if you don’t… [Rhonda]: You can just do a little bit, right? [Jed]: But you can do a little bit, yeah. [Rhonda]: And what about the mustard seed? [Jed]: Mustard seed has isothiocyanates. It has glucosinolates, rather. Sinigrin is the name of the glucosinolate
it’s rich in. It produces a compound called allyl isothiocyanate
and it has myrosinase. And so, yes, you can grind up mustard seed
and use that, too. [Rhonda]: Mustard powder and put it on your
broccoli after you… [Jed]: Yeah. I don’t know. I suppose most mustard powder is okay, but
it depends on how long it’s been stored. I mean, as long as it develops a bite when
you eat it, it should have active myrosinase. [Rhonda]: Okay, yeah. I guess the other thing would be taking some
of these supplements like glucoraphanin, taking it, eating it with your cruciferous may even
enhance because the cruciferous, the raw cruciferous theoretically would have myrosinase. So if you’re taking your supplement with the
cruciferous, you may also be getting the biggest bang for your buck, as well. [Jed]: Yeah, yeah. Well, that’s what this…Nutramax, the supplement
company, was trying to do, I think, is to develop to co-deliver myrosinase from a known
source, known purity and potency with glucoraphanin. But it’s a supplement, not a food. Yeah, I think if I were shunning all supplements,
yeah, I would eat broccoli or broccoli sprouts. Well, if you eat fresh sprouts, they’re fine. Oh, you mentioned that your freeze broccoli
sprouts. [Rhonda]: I wanted to ask you about that. [Jed]: So as you freeze them, this is interesting,
you freeze them, you take them out of the freezer. If you put them in a blender and make a smoothie
right away, then the myrosinase is going to act in that liquid, and so you’re going to
be getting plenty of sulforaphane, I think. If you let those sprouts thaw out, there’s
a bunch of juice that’s going to run out. They’re going to look like a slimy mess, right? So, by the time you see that juice and either
pour it off, or pour it in your container, probably most of the myrosinase activity has
occurred and sulforaphane has probably started to bind to proteins and macromolecules in
that vegetable mess. And because what happens is when you freeze
the plant tissue, when you thaw the plant tissue, I guess, you’ve broken down all the
cell, many of the cells. So the lignin, the structure on the outside
of the plant cells is still there, but the cells are trashed. [Rhonda]: Is that why freezing increases sulforaphane,
it’s just breaking it? [Jed]: Well, ice crystals are forming, yeah,
it allows the enzyme and the substrate to come into contact, form sulforaphane. So it’s probably okay, but you have to capture
all the juice or the easiest thing is just throw it in the blender right way, which is
probably what you do. But it’s interesting because friends in industry,
and in fact, we were wrestling with this. We have a freeze dryer. We have a beautiful freeze dryer that we were
actually given by a Japanese sprout company as sort of thanks for what we’ve done that
allowed them to build a business in broccoli sprouts. And this freeze dryer has trays. And you can put, say, five pounds of sprouts
on the trays. But what you have to do is you have to freeze
the sprouts first and then put them in the freeze dryer, pull a vacuum, and it winds
up pulling off all the moisture. If you stick the trays in a freezer dryer
and pull a vacuum and it winds up puling off all the moisture. If you stick the trays in a freezer and freeze
them and then move them into the freeze dryer, basically what you’ve done is allowed all
the cells to break the thaw as you’re pulling a vacuum. And when we looked at those freeze-dried sprouts,
they had no glucoraphanin, and no myrosinase, and no sulforaphane to speak of because it
had all reacted and then it was just a mess. So there is value in thinking a little bit
about how that enzyme behaves before your start making a thing. You can actually freeze dry broccoli sprouts
very nicely as long as you deep freeze them, or quick freeze them and maintain them in
a frozen state when you go to dry them. [Rhonda]: And that will retain the sulforaphane. The myrosinase. [Jed]: The myrosinase is not coming in contact
with the glucosinolate then. [Rhonda]: Okay. [Jed]: Yeah. It’s a complicated story. Probably wasn’t worth telling. [Rhonda]: Well, it kind of made me think of
something else and that is I’ve noticed when I’ve made my broccoli sprout smoothie, after
blending it, if I let it sit in my cup for a prolonged period of time, it tastes different,
like there is…and I don’t know if that’s the sulforaphane or the sulforaphane nitriles
or what chemical reaction is going on there. But it tastes different than if I just blend
it up and drink it immediately. [Jed]: 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. [Rhonda]: Do you have any idea how long, what
the temporal sort of timeline in minutes? [Jed]: 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 Oregon Freeze Dry, we added daikon sprouts, homogenized and let the stew
sit for 2 hours to get complete hydrolysis. You can do the calculation of sort of the
half-life of the enzyme and how fast it works. And so it certainly, it 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 glucosinolates. [Rhonda]: It does get more foul-tasting, as
you had said, It does. [Jed]: 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. [Rhonda]: Really? [Jed]: 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, appear
in the blood within 10 minutes of ingestion. [Rhonda]: That’s pretty fast. [Jed]: And when you talk to a gastroenterologist
about gut transit time, it stands to 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, but… [Rhonda]: Do you know how long? So, for example, if I drink my broccoli sprout
on Monday, I’m going to activate Nrf2 while I have some of these metabolites glutathione,
things like that. How long does that reaction occur before then? Like, 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. You know, do you have to take it every day
or do you think that’s sort of overkill? Does it last longer? Do you have any idea? [Jed]: I think you are perfectly healthy. You’re good. No, I think you should be fine. Again, we don’t know enough, but it’s apparent
certainly in animal systems and in the limited number of cases where it’s been looked at
in people. It’s not like taking a drug. It’s not like taking an aspirin, which is
going to be flushed from your system and the pharmacokinetics look like this and they are
there, it appears, its metabolites appear and it’s gone. What you are doing when you take sulforaphane
is you’re up-regulating a bunch of enzymes. And those enzymes have a rather long, comparatively,
a rather long half-life meaning they don’t lose their punch. They don’t get deactivated or get broken down
all that fast. And their half-lives are on the order of days,
maybe even weeks for some of them, but certainly a few days is a reasonable guess for many
of them. So once you boost all these enzymes, they
stay up-regulated, in other words, more active for a period of time and then it goes away. So that reminded me I wanted to come back
to the issue of probiotics. It seems there was something we wanted to
talk about probiotic-wise that we didn’t get to. [Rhonda]: I think we were just trying to figure
out whether or not taking probiotics would potentially increase the bacteria that contain
myrosinase in the gut. I mean, the conclusion that I came to was
it’s possible depending on the type of probiotic you’re taking, but obviously, general gut
health and good gut health, and you’re feeding your bacteria the right foods so that they
flourish, as well, is important. Not taking antibiotics. [Jed]: Yeah, I think we covered that. [Rhonda]: Yeah, I think we covered quite a
bit. I am so thankful that we got to speak today
because, I mean, I could just keep asking you so many questions because I’m very interested
in sulforaphane, as you can tell. [Jed]: 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. We missed something. Urinary health. Well, urinary health meaning, really, bladder
health, I think. So we’ve been involved with about 25 separate
clinical trials looking at sulforaphane or glucoraphanin. And in fact, you can… I’m happy to give you a list of them you can
post with this webinar and there are about twice as many clinical trials that we plus
whoever else has been working on it around the world has done. So 55 or 60 clinical trials, all told. Almost all of the trials, in fact, all of
the trials that have been published to date, and when I counted them the other day, they
were about 30, I think, publications on clinical trials with sulforaphane or broccoli sprouts,
all of them have had positive effects to one degree or another with one exception and that
was, unfortunately, a large trial on COPD, Chronic Obstructive Pulmonary Disease, that
we were involved with that just didn’t show an effect. We think we know why now. Hindsight’s always great, of course. We think those lungs were probably just in
such bad shape that they couldn’t have responded. But one of the trials that you won’t see a
publication on, that I’m very sad did not get to completion and did not really accrue
enough patience and I hope we can find collaborators to do a trial on this, is bladder cancer prevention. And, again, I go back to my old friend Yuesheng
Zhang at Roswell Park Cancer Institute in Buffalo. He made the observation many, many years ago
that, gee, when you think about how sulforaphane courses through the body, it winds up being
excreted in the urine as either sulforaphane free and clear, or the majority of it comes
out as its conjugates with glutathione, one of the main antioxidant peptides in the body. Glutathione or acetylcysteine sulforaphane,
a variety of sort of antioxidant, glutathione-derived conjugates. And all of them have some activity in up-regulating
Nrf2, also. So what happens? Go in here, you eat sulforaphane or you ingest
it or you can even put it on your skin. We’ve done a number trials showing protection
against ultraviolet radiation. It gets metabolized, it gets excreted. How does it get excreted? In the urine. What happens to urine? It hangs around in the bladder. So what you wind up having is a high concentration,
relatively high concentration of both sulforaphane and its active metabolites in the bladder
bathing that bladder epithelium and it’s only, obviously, periodically released. We think it would be the perfect place to
demonstrate protection against cancer or cancer prevention. And so we actually had permission for and
started and only accrued, I think, only enrolled, I think, one or two subjects a trial in which
we were to look at just that. And these were people, where we were looking
at secondary reappearance of bladder cancer. So they had had a tumor removed that had cystectomy
and we were looking at the health of the bladder and levels of Nrf2 in bladder tissue that
was acquired by biopsy. So that was the design of this study. As I say, it didn’t happen. We’re actually trying to get one off the ground
with dogs now. Dogs are a little different because they sort
of pee when they want to. So there’s probably not the same constant
reservoir of sulforaphane and its metabolites in the bladder, but certainly to a degree,
there will be. It’s also harder to collect the 24-hour urine
on a dog and to do some of the interventions. But so we are trying to get a canine bladder
cancer prevention trial off the ground. And as I say, we’d love to see it done in
humans because it’s…if there was a gimmie, that’s a gimmie. I mean, it’s got to work there if it’s going
to work anywhere. [Rhonda]: The epidemiology is so strong showing,
I mean, I can just, study after study after study showing cruciferous intake raw broccoli
it’s showing…and preventing bladder recurrence, as well. People that are eating these foods, it’s not
a clinical trial, but it’s just associative data. And there’s been animal studies with bladder
cancer where they give them some carcinogen and sulforaphane in it. So I agree with you. I mean, it would be really nice to see an
actual clinical trial done in humans and it does make perfect sense. Prostate cancer is another one that seems
to also sort of go hand in hand. I mean, the prostate and prostate inflammation
seems to be lowered and one study is showing that men with prostate cancer that were given
pretty relatively high doses of sulforaphane, it slowed their doubling rate of the PSA by
86%. So, I mean, that’s pretty significant. [Jed]: Yeah, yeah. So there are two prostate cancer studies…well,
there are probably more. But Joshi Alumkal at OHSU did one and Bernard
Cippola in France using, actually, the supplement. So Cippola’s study used, where he showed a
dramatic reduction in the trajectory of PSA numbers was in, used… What’s it called? [Rhonda]: Prostaphane? [Jed]: Prostaphane, thank you. Yeah, the French supplement. And Alumkal’s study used our homemade broccoli
sprout extract. You mentioned the animal studies. We actually were partnered on three or four
animal studies with Yuesheng Zhang and Rex Munday in New Zealand. And it was extremely impressive to see the
difference in bladder cancer. [Rhonda]: Right, tumor size. [Jed]: Tumor number, tumor size and number. [Rhonda]: I mean, it was. I saw the publication, extremely robust. [Jed]: Yeah. Nice, gross color pictures, too. [Rhonda]: Yeah, I’m convinced, yeah. You know, and the other thing is smokers. Smokers get bladder cancer and that, you know…I
think, first of all, people that smoke should quit smoking first and foremost, but if they
don’t quit smoking, I mean, I think they should be consuming broccoli sprouts like nobody’s
business because they’re accumulating so much benzene and all sorts of carcinogens. [Jed]: I used to know a seedsman, a guy who
ran a seed company and he smoked like a chimney, smoked cigarettes, and when he learned about
the broccoli sprouts story, he would eat a handful of broccoli, toast a handful of broccoli
seeds and eat them. And he claimed that he was doing that to counterbalance
the cigarettes. I couldn’t advise him on that. Well, you mentioned benzene a number of times
and we didn’t talk about the China studies but with our colleague, Tom Kensler, and many
others, we did a series of studies over the years starting in about 2002. Interestingly, it started out in an area of
China, a subsistence farming area just north of Shanghai where there was a lot of aflatoxin
exposure. And so we were looking at liver cancer risk,
looking at biomarkers of liver cancer and excretion of aflatoxin adducts vis-à-vis
intake of sulforaphane. Over time, as those studies progressed, there
was a series of studies. The liver cancer risks started to come down
because they were exporting their contaminated grain to other parts of China from this region,
and with globalization, they were importing more and more food. So their diet was becoming less aflatoxin-rich. But at the same time, of course, air pollution
was going through the roof. And so the most recent of those studies we
published in 2014 showed, really, a dramatic enhancement of the clearance of benzene, and
acrolein, and other pollutant conjugates in lockstep with broccoli sprout extract consumption. [Rhonda]: It was a 60% increase in excretion,
which is just phenomenal. And it convinced me, like it definitely is
a problem not only in China, but… [Jed]: India. [Rhonda]: India, yeah. I mean, but we’ve got air pollution here in
the U.S. and I live next to a busy street. And I see all sorts of things accumulating
in my place, you know. So I’m taking that for my benzene excretion,
as well. So it’s very powerful and it was just within
24 hours. [Jed]: It’s a dramatic effect and there… So that’s an interesting public health dilemma. You can tell someone not to smoke. You can sort of say in the back of your mind,
I would never say this out loud, but in the back of your mind, you can say, “They had
it coming. The idiots wouldn’t stop smoking.” We never say things like that. It’s not politically correct. But with air pollution, you’ve got…I mean,
people are trapped whether it’s highly educated people like you that are living on the street
where you know there’s pollution or people in the developing world where, you know… [Rhonda]: You have to breathe. [Jed]: You got to breathe. [Rhonda]: You have to breathe and air pollution
is… [Jed]: You got to eat, and breathe, and sleep,
and we can go on. [Rhonda]: Yeah. it’s becoming… It’s an increasing problem and I’ve seen just
more and more studies. You know, a lot of people have focused on
the effects on respiratory inflammation and those sorts of, which are very obvious. But like I said, the other health disease
risk that’s really becoming evident with air pollution is actually heart attacks and stroke
because it’s causing… It’s low-level chronic inflammation. You know, and that’s, of course, where sulforaphane
shines. You know, I mean, it’s inhibiting NF-KappaB
pathway, like you said, activating all these anti-inflammatory pathways. So it seems like a no-brainer. It would be nice to get something like that
into China and India, broccoli sprout. Well, I guess in India, they’ve got moringa. [Jed]: True, true. So if I were doing a sort of a similar sister
study to the broccoli sprout air pollution study in India, I would want to do it with
moringa, I think. Just like we’re actually trying to get two
new autism trials off the ground in the tropics, one in Bangladesh and one in Israel, and moringa
thrives in both places. Of course, in Israel, I can get broccoli sprouts
easily also because there’s electricity and refrigeration. But on the other hand, we may have a better
evaluative network of psychiatrists that can sort of help with the evaluation. So yeah, pick your plant, pick your poison,
and there’s a pairing to be made. I’m sorry we talked a lot about sulforaphane
and broccoli sprouts that makes us seem like a one-stop-shop, but in a way, you can only
be expert on a few things in this world, right? [Rhonda]: Right. Well, the cruciferous family as you mentioned,
there’s over…was it 500 different genuses or something like that? I mean, most people are familiar with broccoli,
cauliflower, kale, Brussels sprouts, cabbage, mustard greens. [Jed]: Yeah, mustard greens, yeah, Kohlrabi,
rutabaga, watercress, wasabi. [Rhonda]: That’s right. Watercress, wasabi. But broccoli sprouts are unique in that they
actually have higher amounts of glucoraphanin, and that was sort of… [Jed]: Very true. One thing that I always tell my class…the
classes that I teach when we talk about phytochemistry. You know, it’s, of course, easy for me to
drone on about what we’ve been talking about for the last hour or so. But it’s important for people to realize that
there are many, many, many other biochemical mechanisms that other plants and other phytochemicals
target. And so there are plenty of other good vegetables
and fruits and there are plenty of reasons for eating them that don’t have anything to
do with Nrf2, and they could be the subject…I hope they’re the subject of another webinar
that you do with someone else that knows about them, for instance, the berries. [Rhonda]: Right, and the cyanines and… Absolutely, I’m interested in all of them,
but I’m particularly interested in broccoli sprouts so I’m extremely excited to have this
conversation with you. [Jed]: I’m going to have to have frozen sprout
smoothies one of these days. [Rhonda]: You know, like I said, you add a
little bit of ice, too, also just so it’s like… Something about the cold, like, helps negate
the bitterness that, like… [Jed]: The flavor, the head doesn’t come out. [Rhonda]: So but I think it’s also very mental. I do notice a mental effect, as well, like,
there’s something kind of nootropic about it where all of a sudden, you’re just more
focused, and I don’t know. It could be completely placebo. [Jed]: So tell me, some people…many people
that I’ve heard will talk about certain drinks or nutritional products or supplements and
say it gives them more energy. Other than eating carbs, eating sugar, eating
a Clif pack, gel pack, or something, I don’t get that. I don’t get that with broccoli sprouts, for
example, and I’ve heard people say, “I’ve got more energy from eating broccoli sprouts.” Do we have a good answer to that someplace? [Rhonda]: I don’t know if we do. You know, I think that the reducing of inflammation…inflammation
drains your energy. I mean, it’s a very energy consuming process. When you’re activating immune cells, that
requires ATP immune. So I do think that we can make an argument
for it, but how immediate that effect is, I don’t know. [Jed]: It’s a little more long-term. [Rhonda]: You know, I’m not sure. I do know that drinking…I don’t know, have
you had a smoothie with the broccoli sprouts before? [Jed]: Yeah, I’m not a… [Rhonda]: You haven’t noticed anything? [Jed]: No, I never get more energy. Really, I mean, I’ve never found a food that
gives me more energy. I suppose…I mean, sugar, I guess, does,
but, yeah, sugar does. [Rhonda]: Sugar does. [Jed]: But that’s not really ideal either. [Rhonda]: No. Well, unless you’re eating fruit, and berries
and things like that are good. [Jed]: Yeah. If we’re going down a path that’s going to
get us nowhere, though. [Rhonda]: Well, I would like to mention for
people that want to follow up on your research and all your publications and things like
that, you have a website called [Jed]: Chemoprotectioncen-,… [Rhonda]: Oh, [Jed]: Let’s call it up and be sure. [Rhonda]: Yeah, it’s,
I have it right here. [Jed]: Okay, yeah. [Rhonda]: So you want to tell us a little
bit about…so that’s your website? [Jed]: Sure, that’s the website of our group
here. This is, we’re speaking in the Cullman Chemoprotection
Center, which is a center devoted to the study of plants and phytochemicals for prevention
of chronic disease and other ailments. And we have a website. There’s a donation box on it. We are always eager to solicit donations from
people who think like we do. We are funded from grants and the largess
of wonderful, interested people. We have a list of our publications on this
website, most of them are clickable. You can at least get to the abstract. We’re happy to send any of our publications
that the general public can’t get, can’t find by clicking. Some of these are copyright-protected and
we can help you out with them. And our website says a little bit about our
mission. So we encourage you to… [Rhonda]: Great. Again, that’s And you’re also on Twitter. You’re not very active, but you do have a
Twitter handle. That Twitter handle is @jedosan, or J-E-D-O-S-A-N. So if you decide to become more active on
Twitter and tweeting things, then… [Jed]: What’s Twitter? We also are on Facebook, The Chemoprotection
Center. [Rhonda]: Okay, great. Chemoprotection Center is
also on Facebook. Excellent. Well, thanks again, Jed. I’ve really, really enjoyed this conversation. I’ve learned a lot. [Jed]: As have I. As have I. Thanks.

Randall Smitham



  1. FoundMyFitness Posted on January 6, 2017 at 5:00 pm

    In this 2-hour and 30 minute interview, we discuss…
    • 00:00:00 – the early history of sulforaphane research, including key initial discoveries.
    • 00:00:37 – the serendipitous unfolding of events that lead to the converging of the research on the NRF2 stress response pathway with the sulforaphane-related research going on at the same institute Johns Hopkins.
    • 00:05:06 – why cruciferous vegetables bother to create isothiocyanates in the first place.
    • 00:07:26 – the involvement of the heat shock proteins, in addition to the increased activity of Nrf2, as an additional cellular response mechanism that's been observed in association with sulforaphane.
    • 00:08:11 – how sulforaphane affects a diverse array of biochemical processes from glutathione synthesis to elimination of reactive oxygen species and detoxification of harmful compounds, including carcinogens.
    • 00:15:01 – whether or not to cook your cruciferous vegetables.
    • 00:15:34 – the epidemiological (associative) evidence that cruciferous vegetable consumption may help reduce the risk of cancer.
    • 00:18:30 – the extremely unpredictable nature of endogenous conversion of glucoraphanin (the precursor) into sulforaphane between person to person.
    • 00:22:14 – practical information surrounding supplementation of sulforaphane.
    • 00:27:05 – the effect one particular french sulforaphane supplement had on the doubling rate of PSA, which is a marker for prostate cancer recurrence in prostate cancer patients.
    • 00:28:17 – the role that the Cullman Chemoprotection Center at Johns Hopkins has played, in addition to fundamental research, in providing early, vital infrastructure enabling some of the efforts of the international research community in elucidating the effects of sulforaphane and related compounds and the underlying biological pathways.
    • 00:28:26 – the incredible, almost geometric growth in new studies that has occurred since the advent of a few of the key discoveries about sulforaphane and its method of action.
    • 00:32:48 – the practicality of probiotics as a way to improve endogenous myrosinase activity needed to convert the precursor to sulforaphane into the bioactive sulforaphane.
    • 00:33:26 – the involvement of our gut bacteria in our ability to convert the precursor of sulforaphane into its active form.
    • 00:37:13 – whether or not endogenous myrosinase activity improves as a function of repeated challenge with glucoraphanin (the precursor to sulforaphane).
    • 00:39:30 – why probiotics may vary in their degree of efficacy.
    • 00:43:00 – why consuming isothiocyanates to reduce the number of bacterial colonies of h. pylori, a risk factor for peptic ulcers and stomach cancer, may turn out to be a better intervention than complete eradication of the species with antibiotics.
    • 00:47:21 – the bizarre relationship h. pylori has with childhood asthma, where it has been shown that having some h. pylori seems to reduce asthma incidence in childhood.
    • 00:52:28 – the effect sulforaphane has on inflammation and why inflammation is often a great therapeutic target for many different diseases, including diseases of aging.
    • 00:54:05 – the life extension properties broccoli has been shown to have in an insect model of aging.
    • 00:59:27 – the underlying causes of Hutchinson-Gilford progeria and the promise sulforaphane may hold for this disease of rapid aging.
    • 01:09:00 – the effects of sulforaphane or Nrf2 activation on diseases of the brain, such as autism (human evidence) and Alzheimer's (animal evidence), possibly through anti-oxidative or anti-inflammatory effects.
    • 01:11:09 – the so-called autistic fever response whereby autistic patients report a sudden reversal of symptoms during brief periods of fever.
    • 01:10:05 – the role heat shock proteins might play more broadly in the prevention of certain neurological diseases.
    • 01:19:00 – the challenges inherent in clinical trials where scientists may be extremely optimistic about the effects that might be observed, but still have to exercise caution and choose trial conditions that may be conservative, for the good of the people whose lives and hopes hang in the balance.
    • 01:27:01 – the role of inflammation and depression and what some studies on animals have demonstrated in terms of sulforaphane's potential as an antidepressant.
    • 01:42:30 – a special isothiocyanate-containing plant known as Moringa or sometimes referred to as the drumstick tree or the horseradish tree.
    • 01:46:32 – Dr. Fahey's inadvertent foray into the consumption of exotic meats during a visit to Africa.
    • 01:51:15 – a compound commonly associated with broccoli: indole-3-carbinol and its downstream product diindolylmethane (DIIM).
    • 01:57:00 – the practicality of using mustard seed powder as an extra source of myrosinase, possibly for your cooked cruciferous vegetables.
    • 02:00:13 – whether or not it makes sense to freeze broccoli sprouts in order to extend their shelf life, and possibly even increase sulforaphane within certain contexts.
    • 02:05:25 – Dr. Fahey's thoughts on where endogenous conversion of glucoraphanin occurs in the body, as well as how long it takes before sulforaphane metabolites hit the bloodstream after ingestion.
    • 02:07:25 – Some general thoughts on frequency in terms of how often one might need to take sulforaphane to elicit its biological effects.
    • 02:12:16 – why sulforaphane may one day be a component of sunscreen.
    • 02:12:31 – what some of the upcoming trials involving sulforaphane are at the Cullman Chemoprotection Center.
    • 02:17:07 – the incredible way in which a sulforaphane-rich broccoli sprout beverage was shown to dramatically enhance the detoxification of benzene through excretion: one study showed up to 61% starting immediately after supplementation.

  2. brian fitzgerald Posted on July 10, 2017 at 5:15 pm

    If you want a great source of probiotics get a pickl-it jar and grow your own cut up your vegetables put them in a the jar poor in a 2% saline solution using Himalayan pink salt It creates an anaerobic environment and in 7 to 10 days you will have trillions of usable probiotics Good Luck

  3. ApoE-ε2/ε3 Posted on July 29, 2017 at 6:08 pm

    Have you read this study?
    Toxicity symptoms following acute sulforaphane treatment in mice. Jul 01, 2017

  4. SomeStickyIky Posted on August 11, 2017 at 3:59 pm

    If you juice the sprouts, will you still get the good stuff?

  5. ctguitarguy Posted on August 15, 2017 at 3:53 pm

    Glucoraphanin supplements match broccoli sprouts for sulforaphane bioavailability: Study

    Also one concerning study: It suggests that it does a number on male libido (much like propecia does, which was a prostate cancer treatment drug). This is concerning of course…

  6. phantumgrey Posted on October 17, 2017 at 5:47 pm

    She loves her Isothiocyanates. It's her favorite word I believe.

  7. phantumgrey Posted on October 17, 2017 at 6:29 pm

    I'd love to know if there is a way to supplement with a good broccoli sprout. The whole making broccoli sprouts is labor intensive when compared to everything else i have going on and NO I don't watch TV, I really am that busy.

  8. Caroline Wilhite Photography Posted on October 27, 2017 at 11:10 am

    I've been taking Broccomax daily for three years for melasma. I realized that it also cleared up my early COPD symptoms. Also, I haven't had a sunburn since taking it, and I never wear sunscreen although spending many hours in the sun on Oahu and in Florida. Consuming sugar (even fruit) and alcohol deactivate the positive effects, and my lung problems return quicker than if I stop taking the supplement. Broccomax is more effective than eating broccoli sprouts from my experience.

  9. GoodGoy Productions Posted on October 29, 2017 at 6:06 pm

    My new go to snack? Raw broccoli with sprout powder in a whole mustard seed, mustard sauce. Super legit

  10. This Is Slammin Posted on November 8, 2017 at 1:00 am

    Wow! Great info

  11. This Is Slammin Posted on November 8, 2017 at 2:02 am

    I love these videos! Unfortunately I will have to watch them a couple times with notebook in hand. 2+ hours well spent. 🙂

  12. GMBCATASTROPHE Posted on November 9, 2017 at 11:31 pm

    What is the best way to eat these sprouts for the medicinal effect?

  13. William Williams Posted on November 15, 2017 at 11:51 pm

    Those big round seeds do not look like my broccoli seeds.

  14. Carl Senden Posted on November 25, 2017 at 8:10 am

    ttps:// I use these and they are backed up with literature. I have spoken personally with a scientist from the company, and she seems passionate about nutrigenomics and health at a cellular level.

  15. Alan Whitton: Coaching - Therapy - London Posted on November 25, 2017 at 3:18 pm

    Dr Rhonda, is there a seed consumption protocol you think I could experiment with at my own risk obvz. Milling seeds first with nutribullet then adding to smoothie. Would a quantity of 20g be sufficient? Only mention that as it's the amount of flaxseed and chia I use too.

  16. Jenna Ryan Posted on December 8, 2017 at 5:04 am

    Where can I get broccoli seeds?

  17. H Berry Santi Posted on December 29, 2017 at 2:49 pm

    In philippines, we cook Moringa in chicken soup or with monggo (moong soup). It is the only vegetable i eat when i was young.

  18. Michael Murphy Posted on January 8, 2018 at 1:41 am

    Seriously, thank you so much Dr. Patrick. After listening to your podcast I’ve lost 45 pounds. My life is filled with energy and I feel like I have a new lease on life. You are such an inspiration and we are all lucky to have you as a resource. Thank you so much again and I’ll never give up my broccoli sprouts!

  19. Zzzzurf Posted on January 11, 2018 at 3:43 am

    Since I started eating these Luciferous vegetables, I feel more angry?
    I have more sprouting in my forehead.

  20. Outdoor Cooling Systems Posted on January 28, 2018 at 3:59 pm

    Your sulforaphane videos have turned me into a health geek. I'm blown away by this info! Even bought broccoli sprouting kits for my friends and family and forced them to watch some of your videos.

  21. Todd Sloan Posted on February 1, 2018 at 7:03 pm

    Well paced for my enjoyment… good team!

  22. josh wurzbacher Posted on February 1, 2018 at 10:14 pm

    Dr Rhonda you are soooo fine. Pretty with a fierce intelligence is a killer combo.

  23. Riptide 10x Posted on February 6, 2018 at 3:11 am

    I read somewhere that a study in mice showed that sulforaphane lowers testosterone. Have you noticed any negative effects in your husband Dr. Patrick?

  24. bigrhom55 Posted on February 16, 2018 at 12:39 am

    What a great guy

  25. Paul Spring Posted on February 17, 2018 at 8:40 pm

    Dr. Fahey is incorrect.  I put broccoli seeds in my coffer grinder and the powder actually has a pleasant nutty flavor – not particularly bitter to my taste at all.  Can easily see sprinkling on my oatmeal in the morning or smoothy.   Sprouting is a pain.

  26. Chad Timblin Posted on March 5, 2018 at 4:05 pm

    Awesome interview. I was particularly struck by Dr. Fahey’s apparently high level of self-awareness and communication skills (e.g. he communicates very efficiently with little filler words and provides helpful sentence cues about where he intends to move the conversation).

  27. JoeKickass324 Posted on March 7, 2018 at 8:12 pm

    Rhonda is so hot talking about broccoli sprouts

  28. Miguel Javier Ayup Posted on March 11, 2018 at 6:58 pm

    Far, one of the best dialogues showing all the life behind this topic

  29. Dave Posted on March 24, 2018 at 3:22 pm

    If freeze-dried sprout powder was put in gellcaps, why can’t this be done for cold-ground seed powder to up the sulforaphane/gram and to avoid the bitterness?

  30. Andrew Christie Posted on March 24, 2018 at 10:20 pm

    does anyone know if grinding broccoli seeds with a pestle and mortar would be an efficient way in releasing myrosinase and glucoraphanin? and would taking the powder be bioavailable ?

  31. Brian R Daeger Posted on April 24, 2018 at 4:32 pm

    So are broccoli seeds better than sprouts or he saying that if its not sprouted into a plant it wont produce sulforaphane? I am thinking about crushing the seeds for my smoothies.

  32. Kenneth Jones Posted on April 25, 2018 at 6:17 pm

    Good science deserves its love. Keep up the good work, please, because I have personally benefited -within two months of YouTube suggesting, first Wim Hof, which led to Dr. Rhonda's online collaborations.

  33. creaturelive Posted on May 22, 2018 at 1:01 am

    Does anyone know if sulforaphane is also goitrogenic?

  34. Kanacho Min Posted on May 22, 2018 at 7:49 am

    There are quite a few animal or in vitro studies on Sulforaphane but still i am reluctant to be a advocate because human trials are stil scarce.

  35. jerry don Posted on May 24, 2018 at 5:34 am

    Dr.Patrick is so beautiful and hot. You are my goddess

  36. Fawzi Yassine Posted on May 30, 2018 at 1:43 pm

    At 2:00:20 Dr. Fahey mention that frozen broccoli sprouts should be consumed without letting them to thaw. I did not understand the reason for that even though he did try to explain. And what confused me Mostly is when he said at 2:01:45 that it is OK to do so as long as you include the juices in. Can somebody explain?

  37. Carlos Ulloa Posted on June 3, 2018 at 3:54 am

    thank you for this wonderful information.

  38. MARVIN FERGUSON JR Posted on June 12, 2018 at 3:42 pm

    Any new information coming from the studies that he spoke about starting around the time of the podcast?

  39. matt gruber Posted on June 14, 2018 at 7:42 pm

    So i ground a teaspoon of seeds in a spice grinder and mixed the powder with an ounce of peanut butter. tasted good, sort of like crunchy PB. will i now live to be 100? Is this all i have to do? next time i'll wait 10 minutes before eating for the sulforaphane to get stronger. Thanks for the info!

  40. Hal Asimov Posted on June 16, 2018 at 11:08 am

    Dr. Greger talks about ways to cook broccoli after chopping it so that the conversion to Sulfuraphane happens before cooking it. Or eating a little raw with your cooked to maintain the enzymes needed for conversion

  41. Bob Bach Posted on June 20, 2018 at 6:18 am

    So much valuable information….. thank you Rhonda & Jed. Based on this, & living in Paris, I went on a hunt for Prostaphane. I picked some up at the only reseller in Paris.. expensive!, but I thought I would give it a go to see if it might help my nightly asthma (aggravated since I arrived here) So far so good.. 1st night no asthma… will update, after more usage. (Update, a few weeks later)…After a couple weeks use, off and on I decided I will not buy again. Expensive, and it seems to push my mood to the darker glass half full side, so much so that I am weary of taking it (take in the evenings) for fear of having another down day. Also it has blue dye, why did anyone think that would be
    a marketing plus? It does seem to raise my body heat at night, and seems to give stronger dream recall.. However it seems to push my overall state to feeling a little crappy, which could be the hormesis effect Rhonda mentions. After I finish this (or give up on it) I will just continue with Moringa.. which doesn't seem to cause the negative effects mentioned. No real change of nightly asthma noted but this would require a longer experimentation to be certain. (2nd Update 2 weeks later) I took a week break and my mood was relatively well. Took it last night around 8pm. This morning the depression truck hit me. No motivation etc. I will give up on it.. stick with Morninga or sprouts. An expensive test.

  42. Taisa Foster Posted on June 20, 2018 at 3:18 pm

    Dr Abram Hoffer discovered long ago that most mental illness is caused by a deficiency in Niacin and can be cured with fixing the digestive system by removing inflammatory foods and adding Niacin. My bipolar is gone now because I did just that. I use nutritional yeast tablets to get the all the B’s.

  43. yourbeamofsunshine Posted on June 27, 2018 at 12:48 am

    Thank you for this wonderful video. I know I will watch it many times to assimilate all the information.

  44. Andrea Bancone Posted on July 13, 2018 at 4:01 pm

    The product description of prostaphane says it is only aimed at men aged +45 to treat prostate diseases . Would it make any sense to use it as a supplement ?

  45. Jared Flanery Posted on July 18, 2018 at 2:27 am

    love the comment on so-called developing countries, great interview!

  46. D D Posted on July 18, 2018 at 10:14 pm

    I really prefer just crushing the seeds and putting them in capsules. Its is so much easier to make and take everyday. I heard that their could be negative effects to doing this though. Has anyone else heard of something similar?

  47. MrBoomie00 Posted on August 23, 2018 at 1:09 am

    Holy cow, where has she been hiding those?

  48. ChuckleberrySoup Posted on September 16, 2018 at 3:26 am

    Is it better to use shredded Moringa leaves rather than the ground powder?
    I note Dr Fahey observed that there is an optimal period for Myrosinase interaction with the Glucoraphanin to produce freeform Sulforaphane, once the cells have been crushed in the freezing process of Broccoli sprouts

  49. Dylan Nance Posted on September 16, 2018 at 10:25 pm

    Does she have research on CBD and the combination of the gene sequence activation and possibly boosting it with CBD?

  50. burned oils Posted on October 1, 2018 at 2:40 pm

    i luv her big lolos lol she prety happy to make sure that her camera shows them loll even tho she has an husband he he(can never trust females)

  51. Meshak VB Posted on October 7, 2018 at 7:49 pm

    I did not intend to watch this whole video. Somehow it held my interest the whole way through!

  52. HM113 Posted on November 2, 2018 at 2:27 pm

    WOW!!! I will have earned a PHD in Sulforaphane after watching this several times, LOL. A wealth of info. THANKS!!!

  53. Locrian08 Posted on November 13, 2018 at 2:05 pm

    @2:15:00 I guarantee that the majority of Americans are strongly against lab research on dogs that involves exposing them to carcinogens and killing them at the end of the research. It's literally stupid (or more precisely irrational) to experiment on dogs given the risk of protest / backlash.

  54. Kevin Decoteau Posted on November 26, 2018 at 9:19 pm

    So, regarding probiotics, I heard them say the ones to take are refrigerated, what brands and what count of active bacteria should one look for?

  55. Skip White Posted on December 26, 2018 at 4:46 am

    my god she's top heavy

  56. leon kennedy Posted on January 2, 2019 at 10:23 pm

    Rhonda I love your videos. Please don't ever stop. I love how much effort you put into them, from the definitions of terms to the time links to specific topics discussed. Yes yes yes

  57. The Casual Citizen Posted on January 3, 2019 at 3:20 am

    Rhonda Patrick is HOT!

  58. Adiudicium 1776 Posted on January 3, 2019 at 3:21 am

    Fascinating interview! The footnotes and graphs are INCREDIBLY helpful! Thank you so much for all the hard word making these videos. I subscribed!

  59. Sam Posted on January 3, 2019 at 9:38 pm

    " probably published before you were even born " my guuuuuuuuuy

  60. Marion Ake Posted on January 3, 2019 at 9:50 pm

    Have you found glyphosate in the broccoli

  61. Suzanne Lowrie Posted on January 26, 2019 at 10:41 pm

    I’ve purchased freeze dried moringa powder. But is it useful?

  62. Suzanne Lowrie Posted on January 26, 2019 at 10:49 pm

    Moringa noodles and moringa tea are acceptable.

  63. Jacob Gray Posted on March 1, 2019 at 6:37 pm

    I notice you can buy broccoli sprouting seeds from different varieties such as purple broccoli. Do you know which strains are the best?

  64. rkingsiv Posted on March 3, 2019 at 9:06 pm

    14:00 Broccoli seeds myrosinase, 16:31

  65. Epic Winz2017 Posted on March 5, 2019 at 10:24 am

    2019 MILF AWARD 🥇

  66. Laundry Zoo Posted on March 25, 2019 at 5:19 am

    One of the biggest problems with the food service industry is we treat eating as entertainment rather than nutrition. Also food suppression is real. Most people are not growing edibles in their yards.

  67. Laundry Zoo Posted on March 25, 2019 at 6:04 am

    Vivisection is so critically flawed animals can not consent. Adult humans can. Be an organ donor.

  68. Laundry Zoo Posted on March 25, 2019 at 6:16 am

    Yes the Boca Raton Community garden at the library in Florida zip code 33432, zone 9 grows a Moringa tree. As well as cocoplumb with the Womens Junior League. They donate 10% of produce to Helping Hands, a food pantry. You can just go pick some organic moringa pods. They are shaped like snap peas but jelly or guava texture inside. I think bitter.

  69. Brian Smith Posted on April 1, 2019 at 2:20 am

    Poor guy… Had to be pretty tough doing an interview while keeping a guarded gaze.

  70. Diana Tarrant Posted on April 1, 2019 at 11:28 am

    Helico bactor can be controlled with the use of Bovine Colostrum caps. Research done in New Zealand over 20 years ago

  71. Maximilian Eberl Posted on April 12, 2019 at 4:31 pm

    I am not a native english speaher.
    What is this "cole craps" at 0:12_50 ???

  72. brett harter Posted on April 21, 2019 at 8:46 am

    Ive been siving out the seeds wont be doing that again haha

  73. Noga Horovitch Posted on May 6, 2019 at 8:04 pm

    What bacteria are myrosinase containing ?

  74. First Son of Man Posted on May 19, 2019 at 7:57 pm

    Are her boobs really that big? Are they fake?

  75. Kj Jacobs Posted on May 21, 2019 at 7:57 pm

    Anyone else here for Dr Rhonda’s voice? I could listen to her talk all day😍

  76. Tom Sparks Posted on June 11, 2019 at 11:42 pm

    Thank you Dr. Fahey! One brave doctor among millions! Most of the GI docs I deal with still say that nutrition has nothing to do with disease conditions. Amazing. I understand they are protecting their practice, but they are QUITE pathetic doctors who actually think that mouth to anus and what you put in it is inconsequential to health. They are not healers.

  77. Mark Hunt Posted on June 14, 2019 at 11:10 pm

    Can you take too much broccoli sprout extract?

  78. gordon christer Posted on June 21, 2019 at 10:34 pm

    Wonderful ! The exchange of knowledge at this level whatever subject ……..Well gets me off ! 😉

  79. Leadingbrandz Posted on July 8, 2019 at 1:43 pm


  80. Nik Lyons Posted on July 9, 2019 at 6:34 pm

    Does less bioavailability basically translate to more strain on liver and kidneys? Or is that way too oversimplified?

  81. Nik Lyons Posted on July 9, 2019 at 7:27 pm

    It's cool how now everyone can speculate together and comment and share to grasp these overly complicated systems into manageable and hopefully useful ways. Thats crazy about the fever study. I just assumed "fevers" were a reaction to pesticide on processed and store bought food but to truely understand how all these compounds interact and commune is really cool. I normally don't like scientist and doctors but I like these two curious and smart people. They are sticking their necks out even making these videos

  82. lester palocsay Posted on July 11, 2019 at 12:28 am

    dose,dose,done, then lay off then a wham superdose may be the key to getting the effect sort of like throwing a race car into 4th gear, just a thought which in either poppycock or has some metrit.

  83. David M Posted on July 13, 2019 at 6:13 pm

    Thank you for the work that you do in editing these videos. The time stamps for the topics are nice but I imagine you did that as a way to maximize your own understanding of the information shared with you during this very rare encounter ;). Also, overlaying the commentary with the relevant data really puts into context what he's bringing up and helps in grasping what he's discussing. It helps too, that he talks in a very understandable manner.

  84. 714boba2003 Posted on July 21, 2019 at 6:28 am

    I never watch a 2 hr video on YouTube but this was well worth time spent. Thank you both for this valuable insight. Please do more videos on broccoli sprout SEEDS.

  85. Olivia Walker Posted on July 24, 2019 at 1:57 am

    News to me…thanks

  86. Hi Bye Posted on July 25, 2019 at 7:36 pm

    I commend him for going out of his way to not look at those tattys😅

  87. xxx xxx Posted on July 29, 2019 at 10:11 am

    Let me be honest , Indians/Pakistani never consume Moringa leaves in their cuisine, we guys only eat the drumsticks in some curry Trust me !

  88. CVo83 Posted on August 2, 2019 at 3:54 pm

    Curious if you ever tried the broccoli seeds ground up??

  89. ortcloud99 Posted on August 2, 2019 at 6:56 pm

    2 1/2 hours long! I need some life extension supplements just to get through this video!

  90. Adreno2342 Posted on August 2, 2019 at 8:28 pm

    54:20 – Rhonda: "Have you seen this study?"
    Jed: "No"
    Rhonda: "OK, so let me tel l you"
    She is sooooo happy!

  91. DR KIMJIHOON Posted on August 7, 2019 at 4:25 pm

    120:44. Studies use Avmacol for their SFN because its got 35% bioavailabilty and its consistent.

  92. Marans Candy Posted on August 11, 2019 at 5:29 pm

    Differing studies say SFN both depleted glutathione and increased levels of glutathione. Very confusing. Does SFN damage mitochondria or not?

  93. Jack Nguyen Posted on September 19, 2019 at 4:30 am

    Dr. Ronda is hot…

  94. Tom ChimeraLove Posted on September 21, 2019 at 7:33 pm

    Thank you Rhonda and Jed for your amazing and very important work!

    I wonder if lacto fermenting the seeds/sprouts will convert glucoraphanin to a shelf stable form and ready to eat sulforaphane.. maybe even more bio available,
    but maybe instead of lacto fermenting a specific species of bacteria starter should be used, a Myrosinase producing bacteria which would pre-digest for people that don't have enough.
    Also, the fermenting environment should have this main bacteria and other harmful ones hopefully don't survive, like e.coli from unclean sprouting

    I would love to hear Rhonda's thoughts on this

    I just saw on Mercola's website fermented broccoli sprouts,
    They write "…And because we use fermented broccoli sprouts, the conversion to sulforaphane happens before you even take it!…" I wish I could find more information on this

    And this patent:

  95. Mandy LaGreca Posted on September 24, 2019 at 3:41 am

    How is this product?

  96. HazardSports Posted on October 6, 2019 at 11:37 pm

    11:50 exactly what I was thinking- glad you asked!

  97. David Sayers Posted on October 23, 2019 at 5:51 pm

    Thanks for allowing your guests to give long and detailed answers. This way one gets to the logic behind their answers