[Rhonda]: 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 clinicaltrials.gov, which is the government’s database for clinical
trials. So, again, all these studies are looking at
biomarkers of inflammation, as you say, IL-6 is one of the key markers that people are
looking at, COX-2, TNF-alpha. The supposition is that those markers are
going to go down. The supposition is that markers of Nrf2 activation
are going to go up, and heat shock protein markers are going to go up. We’ll see. [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,

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Methew Wade

4 thoughts on “Sulforaphane’s positive effects on brain health and autism | Jed Fahey”

  1. Watch the full episode:
    https://youtu.be/Q0lBVCpq8jc

    FoundMyFitness episode page:
    https://www.foundmyfitness.com/episodes/jed-w-fahey

    More clips from this guest:
    https://www.youtube.com/playlist?list=PLrGxo-5Uw8gIpHS5rH2Z9411ncCsimn5m

  2. It would be exceptionally cheap and easy to simply compare a group of vaccinated vs to unvaccinated children and count which group contains more autistic kids. Just a humble suggestion from one of us lowly non-members of the priesthood. Kinda weird how such a basic, obviously necessary, and cheap study hasn’t been done already but I’m sure it has nothing to do with pharmaceutical companies not giving a shit about us

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