Complementary and Integrative Therapies

Complementary and Integrative Therapies


– Our next speaker is gonna talk about Complementary
and Integrative Therapies for autism and this is Dr. Robert Hendren. Dr. Hendren has been a
speaker at the conference in the past and always does a great job. He’s a professor of psychiatry
and behavioral science, the division of child
and adolescent psychiatry and co-director of the UCSF
Dyslexia and Director of Program of Research on
Neurodevelopmental, Translational, Outcomes Research program, called PRONTO. He is currently applying a
targeted outcomes research approach and collaborative projects with the Oak Hill School
for Youth with Severe Autism and Neurodevelopmental Spectrum Disorders in San Anselmo, California and at the Charles Armstrong
School for Youth with Dyslexia in Belmont, California, and we’re very happy to
have him here with us today. Dr. Hendren. (audience applause) – Thank you. Thanks. It’s a you know, the highest
complement you can get is to be invited back and I
think this is my third or fourth time and it’s a great
conference to be a part of. I think I first came here
many, many years ago when I was at the MIND Institute, and now
at UCSF, and it’s been nice to follow the progress of this as we go along. I I’m going to go, follow the the style of Dr. Sherr and
Dr. Leventhal, which is to go fairly quickly. You have slides in your books,
and for some of the things that have a lot of material, you could look at that in more detail, so that we’ll cover a fair amount of
material as we go along. I do a number of studies, I’m the consultant for different places, most of those are not
things that we’ll be talking about today, but just to be sure that I’ve disclosed everything. There it is. We’re gonna talk a bit
about the definitions of what is now increasingly
called complementary and integrative medicine, but
historically has been called CAM or complementary and
alternative medicine. Talk about models for understanding this, in terms of a potential
mechanism of action, review several promising
biomedical or CAM treatments that seem relevant and
the evidence for those and when we might consider using them. Key points that I hope you’ll
come away with are that families commonly seek
complementary and integrative medicine treatments, whether
you know about it or not. Families often will see two different practitioners, one traditional, one more integrative or complimentary and they may not tell each other for fear that there would be criticism of their doing that and then you don’t know fully what’s
happening with your patient. So it’s important to be open and we’ll talk
about some brief guidelines for doing that. We’ll talk a bit about the
rationale for some of these treatments and their
potential benefits and that’s what really is most important for me. There’s a number of different ideas that range from really wild to having some good rationale. While there may not be good evidence, if there’s rationale I think it’s worth thinking about and considering
and working with parents to think in those same ways. Actually, four agents, ’cause
I added one just last week. That have a rationale for
use with neurodevelopmental disorders and at least one
randomized control trial showing efficacy and safety include
melatonin, Omega-3s, folate and folate was the one that was added a couple weeks ago, and micronutrients. Those that seem to show some promise
are things like NAC, methylcobalamin, and digestive
enzymes and we’ll talk about all of those as we
get toward the latter part of the talk today. CAM has been defined as a
group of diverse medical and health care systems,
practices, and product that are not generally considered to be
part of conventional medicine. I think that’s gradually changing. We used to think that CAM was
something that people would do when they didn’t want to
do what really worked, or when they wanted to avoid things that might have side-effects
but there wasn’t a good rationale for using them. But increasingly, there’s
starting to be a rationale and people are starting to say
“maybe there’s ways that we “can improve the body’s
resilience, that we can improve “the epigenetic processes”
and we’ll talk about those as we go through it. Those ways that we can help the body be healthier, rather
than trying to just stomp out the side, the associated symptom that we want to get rid of. 12% of children in the
U.S. use complementary and alternative medicines;
up to 74% of those recently diagnosed with autism use CAM. The reason, the main reason, are for concerns about safety,
side effects, and those from prescribed medications. The wrong way In talking with families
about biomedical treatments, it’s important to try
to maintain an open mind and to say to people, tell me,
what else are you considering using? What else do you do? And, without necessarily
being critical, use that as an opportunity to instruct them in how to review the
literature, how to think about mechanisms of action. And when they still stay really pretty serious about
saying they want to try this, try to have a way that you at least make sure they’re
seeing somebody that you think is reputable and that you
can have some kind of a relationship with. A number of years ago, a guy who is a neurologist trained
at Hopkins, who has daughter who had autism, came to visit me at the MIND
Institute and we talked. Talked about what things has he tried? And we tried all the conventional things, we went through those, then
we started going through alternative things and then
I said have you ever tried chelation? He said, yes. And I said, I don’t believe
that, Jonathan, how could you try chelation for your daughter? And he said to me, in a way
that I’ll just never forget, he said, “You know, Bob, my
little girl, Hannah, has autism “and nothing that I’ve used is working. “So I’m gonna try everything
that might be able to work “so that I’m sure that
I didn’t miss something. “And I’m doing it in a thoughtful
way, and in a careful way, “but I want to be sure I
haven’t missed anything.” You might know Hannah by her
name, because she was the one child that first won in vaccine court, for her father, Jonathan, having taken her, saying that she had 11 vaccines at one time and
developed autism afterwards and the vaccine court gave
him a couple million dollars. Not that that makes a point,
except the point is that this man, Jonathan, was out
to try everything that might help his daughter and wanted
to be sure that that was being done and so I think
if we can understand that for parents and try and help
them learn to think wisely, we can make a difference in helping them make good decisions. I’m gonna go through a whole
series of all the things that are listed as complementary
and integrative treatments. There’s a website that is on ARI, the Autism Research Institute,
and if you just Google that, ARI or Autism Research Institute,
you’ll find that they have a survey that parents have filled out with a whole series of
things that they’ve tried and they go through rating what
things they thought helped, what things they thought didn’t help, and it includes conventional medications and it includes these more complementary and
alternative or integrated kinds of treatments. But you can see the
medications go from things like diabetic agents, some that
affect purine metabolism, there are things that will affect fungus, viral, antivirals, a variety of non-biologic
treatments as well that can affect the way the
body functions or works. Co-Q10, that might be helpful
for mitochondrial function. Craniosacral therapy, curcumin, digestive enzymes and we’ll
talk about some of these, but many of them have no
evidence other than anecdotal evidence that parents filled
out on this form saying that they thought that
it made a difference for their child. And the list does go on with things that have not shown good evidence,
like hyperbaric oxygen, some that have shown evidence in certain
cases like L-carnosine, methyl B12, NAC, naltrexone, low oxalate diet, probiotics, and going through a variety of vitamins. When I started, when I was
first being interviewed to be the executive director
at the MIND Institute, I was interviewed by four
parents who had started the MIND Institute and raised,
over the time that we were together, at the beginning, $100 million. They said, we want somebody
to direct the institute that has an open mind. We want you to do good
science, but leave no stone unturned about what might
make a difference for people who have autism. And they encouraged me to go
to some meetings that were then called DAN meetings, and learn about these things that people were doing. The first one I went to
was in Portland and I left in the middle of it. I just thought, you know,
there is no rationale for this, this doesn’t make any sense at all. I don’t see why I should even
spend my time trying to learn about it, but I went away and
I started thinking, you know, these people are thinking out of the box. They’re trying to find something that might have some rationale. They’re not researchers,
they didn’t do good research, they didn’t know how to
study those things, but they were trying. And they were looking for
other ways of thinking, and we’ll talk about some
of the studies that resulted from that and where they’ve
gone and I think how keeping an open mind is a
worthy thing to do in this field in trying to figure out how
people might think about what’s happening. Well, as Dr. Sherr said
he was going to tell you in a half an hour what causes autism, I’d say here it is quickly for you. The first is a genetic neurodevelopmental vulnerability,
the kind of first hit. And then the way that that
interacts with environmental stressors and the interaction
between the two of those, so that’s not so simple,
and all the ways that genes interact with each others,
and genes interact with the environment, are then what
leads to that process called autism, but it also suggests
that maybe there are things that we can do for the second
hit that it can improve the outcome of the
interaction between the two. The third hit, though,
comes when we say autism is a hopeless disorder and
there’s nothing we can do to make it better. And, sure enough, if those
people are put in institutions or taken away from the
opportunity to learn from others or other
typically developing kids, they don’t tend to do as well. And so that restricted development
is the other thing that seems to create the bigger problem. In thinking about this
model, you could say if we were to think about
autism as being a slice through the earth, and the
center of the earth is the DNA, that’s the core of the earth, and the symptoms are what
we see on the surface of the earth, you could say,
as we have, historically we first started out
looking at symptoms saying oh we can say we can understand disorders by understanding symptoms
and we created DSM. Then we said, hopefully, that
we can understand disorders by understanding genes
and we’ll find the DNA and we’ll be able to fix the problem. That hasn’t worked
either, and increasingly, what we’re talking about, is trying to understand
the epigenetic process, the endophenotype, what’s happening in the center of the earth. As we say, how can we
affect the metabolic process that comes from these genes and the way they express themselves and then how they work themselves
up to the symptoms. I will tell you that when
I first did this model, I was at the MIND Institute and I said in, I thought a nice
way, to Sally Rogers. I said, you know, Sally, the
problem with what you’re doing is you’re working with
behaviorial treatments and you’re only working on the symptoms, on the surface of the earth. Sally said, in her inimitable
way, “You’re wrong, Bob.” She said “If I get these
kids early enough, and I can “do the right treatments, I
can re-sculpt their neurons. “I can make their neurons
different by what I’m doing.” And she’s shown that in her
Early Start Denver Model work, and the whole team has done looking at MRIs and EEGs and other measures that can say
yep, you are re-sculpting neurons in that way that
you’re doing these things. But as we think about what’s happening in the center of the earth I thought of it as
somewhat like the terroir, that you think of with
a wine, where you say you know, how much clay, how much sand, how much rain, how much sunshine, but I was visiting a
close friend of our family in Alsace and the people
there were talking about their terroir and
said it’s not only that. But it’s also the souls of the people that are tilling the soil that make the terroir,
and make great cepage or great grapes. And I think that was an apt metaphor, I thought, for me in the
way kids grow brains. There’s this kind of soil that what’s happening here
in the center of the earth and there are ways we
can make that healthier and make that work better for kids and I think some of the
things that we’re doing with some of these integrative treatments can make it effort for that to happen. So we might think of
level four interventions being more behavioral, level one genetic, which we’re doing a little bit more of this
Dr. Sherr mentioned earlier, but what I’m gonna spend my time talking about is this area in the center, the metabolic processes and how can we make those healthier
and more resilient. Those kinds of processes are things like immune abnormalities and inflammation or oxidative stress or
disturbed methylation. Mitochondrial function,
free fatty acid metabolism, excitatory and inhibitory balances, hormonal effects in the microglia, which we’re increasingly appreciating in a kinda gut-brain way, have an important role
in the way that the brain functions and works. The problem in much of this research is that these are processes that are going
on at various times. They may be in sequence, they
may be active at one time, so when we try a treatments that is going to work well for immune
function but there isn’t an immune activity going
on because it’s moved into another process, further downstream, like say mitochondrial function,
we may get a negative study unless we have a way
of finding a biomarker that will make a difference
in our making sure we’ve selected the right group
to try this intervention. And I’ll tell you about a
study that we just completed, when I get towards the
end, which is our effort to try to do that. But we need to have a way to know that this process is what’s
active now if we’re trying to use an intervention that’s target it, otherwise we’re just shotgunning and maybe not fully making a difference. But this kind of thinking, this way of looking at these metabolic processes is a kind of paradigm shift. It’s another way of
understanding a disorder that’s not so much based either on genes or symptoms or even brain
structure and function, up at the surface of the earth, but what’s this metabolic process and how can we affect a change with it? There are people that have
intestinal inflammation, digestive enzyme abnormalities,
metabolic impairments. People with autism that show
signs of oxidative stress, mitochondrial dysfunction,
immune problems, and that range have a whole variety of
ranges that we might see improvements by a
combination of nutritional recommendations, prescription
medications and addressing the underlying medical
conditions that we see and that’s what we’re gonna spend our time talking about as we move ahead. First, though, I want
to spend a little time applying this to saying is there anything that we could do to help that process
that we’re talking about from going awry? If someone has a genetic vulnerability, is there a way that we could create the healthiest kind of environment so that those genes
don’t express themselves or don’t start lining
up and having this plant who might be growing towards
the light over here going off, rather than growing straight in a way that could make it healthier. And there are a number
of websites and places that have started talking about this, including ARI, and that’s
where Maureen McDonnell’s recommendations are. We’ll talk about some of those people are saying but, you know, some people are saying things that don’t
have very much evidence. And there are a growing
body of people, though, trying to see what can be done. Looking at the prenatal history, the epigenetic information that’s not contained in the DNA sequence, and how could we think
about that first level out, which is the chromatin patterning and the methylation and how can we then go on to other places where
we can make a difference. Some people even say this
kind of thing gets carried on from generation to generation and might express itself
even at some point later. If you recall the studies
of smoking grandmothers who have grandchildren that
show that same evidence or mouse models that can
actually show seven generations of skipping that makes a
difference before it finally expresses itself in that small embryo and then the fetus. There are things we know affect risk, like older women who are deficient in iron have five times a greater risk
of having a baby with autism. Prenatal steroid perturbations, even in a skipped generation
may increase risk. Preterm birth, small for gestational age, C-section are all associated
with increased risk but it’s not just those
processes by themselves, it’s what might have led to the reason for a C-section. Diabetes, being overweight,
autoimmunity, infection, and age all play a role. Higher maternal intakes
of certain nutrients, seemed, especially folic
acid and to some extent Omega-3, vitamin D, antioxidants,
iron and breastfeeding are all associated with better outcomes. Those have been shown in isolation but so far somebody
hasn’t done one, large, population based study saying
this could make a difference if we took high risk moms,
but there’s one study, that we’ll talk about in a
minute, that took high-risk moms, gave them high doses of
Vitamin D and the incidents of those that took the vitamin D compared to those that
didn’t, was far lower than in those that were not taking that extra supplement. That’s been shown for a
few other things as well and at least suggest,
maybe we could do things, especially in high-risk pregnancies, to say that autism could be prevented. A pediatrician, Liz Mumper,
has a practice mostly filled with kids with autism and she took mothers, 290– mothers of 294 patients, that were wanting to have a second child and she said try these things. Make sure you’re not exposing yourself to environmental toxicants, breastfeeding for a long period of time, at least a year and a half, think about your gut flora composition, look at your nutritional status, she advised against acetaminophen use, even before the recent studies, and used antibiotics sparingly and tried to do what she could to support people with infections. Out of these 294 patients
that she’d followed from 2005 until 2013 none of those kids that
were born came with autism and yet the average rate is somewhere between 17% and 20%. So it’s an anecdotal
study, it wasn’t published in a peer reviewed journal, but it was someone’s practice and there’s one other study
that’s somewhat similar, talking about using
those kinds of strategies to make a difference. There a group that’s called
Preconception to Infancy, P2i, and the website for that is at the bottom, that’s now trying to operationalize this in a much larger way using
step-by-step guidance, based on hard science, that
might increase the odds of delivering a full-term
baby who won’t suffer from chronic illnesses like
those that are listed there. And their goal is to do this
with one million babies. There’s been a new center that’s developed at the University of Georgia,
headed by Jose Cordero. Jose was at the CDC for
quite a number of years, and was a professor both at Emory and the University of Puerto Rico. It’s just getting started and if you want to read more about it in
the things you’re are doing, that’s something to at least
think that this is beginning to move into an area of seriousness that might be able to make a difference. I’m gonna shift and
talk just a little about some of the labs that might be used. Dr. Sherr went through the
ones that are the main ones. The things that are standards,
like a metabolic panel a variety of other
things are the standards, and I see I’m losing my time so I’ll go fast through these, and you can read them if you want, but the latter ones are ones that are somehow though of when a
person has a reason for that. Some of the others, and I guess
I didn’t show all of them, fortunately, so I will go faster. There are a number of other
tests that you’ll find some doctors are doing that
don’t have good evidence and we’ve spent a lot of
time trying to find evidence for some of those tests that
have become fairly expensive, but many of those doctors have a rationale and feel like there’s a
reason that they’re doing it, but you’ll sometimes
see patients that have sheet after sheet after
sheet of a number of tests that they say are, have an abnormal values and that one might do this to treat. That’s not saying that they’re not having good value but they don’t have strong evidence in the
ways that they work. I’m gonna go through this
last part of the talk talking about several
complementary integrative medicine treatments and I
think have some evidence for their working. Melatonin, there was a good
review and meta-analysis of 35 studies saying, and
five of them were randomized control trials, showing that sleep duration was increased and the sleep onset latency was decreased and the night-time
awakenings were unchanged. The adverse effects were minimal to none and I use a fair amount of melatonin for sleep, usually between and three
and nine milligrams. That makes a difference and
doesn’t seem to have harmful side effects, either
short term or long term. Vitamin D became popular when
people first started think, as an ideology for autism
when people said, you know, maybe some of these people
that are developing autism are dark-skinned people that
move into low-light climates and there was a large number
of people from Somalia that seemed to be developing
autism when they moved to the Scandinavian countries. There’ve been also studies
showing that if you live in a rainier environment, there
might be a higher incidence of autism, perhaps because
kids stay inside more. All kind of anecdotal evidence, but we did a small study showing that we could
give doses of Vitamin D and it could, even at high doses, that we had
some trouble getting through the IRB but was, were given
safely and effectively. And there have been two recent,
randomized control trials suggesting that Vitamin D makes a difference in
symptoms for kids with autism, at doses usually between
2,000 International Units and 5,000 International Units. The study that I mentioned
is not up there, but it was done of pregnant moms at high risk taking 2,000 IUs at the beginning, 5,000 through the pregnancy and 7,000 International Units
when they were breastfeeding, finding a much lower incidence
of autism in those offspring. It was an open-label trial, however, and there’re reasons to say maybe
that isn’t fully working. The first study that we thought of doing when the parents gave me this
challenge and I went to talk to these people was they said, I said, what study
do you think we should do that’s a double blind, randomized,
placebo controlled trial. They said chelation. I said, no I don’t want to do
chelation for our first study. That’s just
(audience laughter) too controversial and, it’s too complicated. They say you need to be on a
casein-gluten free diet first, and then there’s all these
things that you’re taking out, as Bennet pointed out, all
these heavy metals and so you have to supplement them
with other heavy metals if you’re gonna do it right. So, I said what’s second? And they said Methyl B12. So we did a study at the MIND Institute of Methyl B12 and I have to
tell you, it was the second kid that we saw in that study that made me passionate about doing this kind of work. This little boy that was, fogged, kind of, looked like there was a veil over him. You didn’t really get a response. He was in another world,
and I think we all see a fair number of kids with
autism, not all of them, but a fair number like that. And he came in and he
started in the methyl B12, and he came in after a month and it was like he’d been awakened. He looked at me and it was as though
he’d just discovered me. And his parents said he’s
more engaged, he’s seeming to, it’s like this veil has been lifted. Now, his autism wasn’t cured but he seemed to do a fair amount better. We finished that study and our biomarker group that
showed oxidative stress were the ones with the most
impaired oxidative stress were the ones that showed
the most improvement. Based on that we got a
grant from Autism Speaks and we did a second study,
which is down at the bottom, that has recently been published that shows, it’s not in press any more. Showing that the active
did separate from placebo in a randomized control trial and the oxidative stress
biomarkers were the ones that were the most predictive
of whether these kids would respond or wouldn’t. Antonio Hardan did a study
of NAC for kids with autism. Randomized control trial
showing that actors separated from placebo. Other groups have done
similar studies with NAC, looking at self-injurious
behavior, OCD-type behaviors, all showing some benefit. We did a study of Omega-3s,
one that was a small study, another that was an internet-based study, so we could enroll people on the internet. We sent them placebo or Omega-3s. While active didn’t separate,
there was a strong trend to Omega-3s making a difference,
and we were giving one gram a day and there are several
randomized control trials done in Europe that show benefits
from Omega-3s for autism. Jim Adams has done number
studies of vitamin and mineral supplements, some of them
randomized control trials, again showing that these
high-doses of micronutrients made a difference in a number of the scales that you can
see on the last bullet, suggesting benefits from high-dose micronutrient supplement. He was using something that
was somewhat like Empower but it was not Empower, but
it was that kind of high-dose micronutrient. Diet has been inconsistent. The studies of casein-gluten-free diet,
there was one early study suggesting benefit but later ones, it’s a hard study to design, have not shown clear benefit. Looking at the microbiome,
studies of mice have shown that creating a mouse model of autism, reversed the autism when given probiotics and there have been several other studies looking at
the value of probiotics. Pancreatic digestive enzymes. A company called Curemark,
who we’re doing a study for, and it’s our second study with
them of a multi-site study saying, I guess, that this caused improvement because the FDA is encouraging them to
go back and do a second study so the FDA reviewed that
data, although it’s not been published yet. And they used as a biomarker
in the first study, fecal chymotrypsin had to be low. The FDA said, how do you know fecal chymotrypsin is a marker, you need to go back and
do the study for all kids. If anybody has an interest in pancreatic digestive enzymes,
we do have a study ongoing at the MIND, one is at the
MIND Institute and one is here. There have been studies,
as was mentioned earlier, vasopressin. Those results haven’t been
produced or published yet either, except that the company, Roche Genentech, went to the FDA and the FDA told them
they wanted more data. So, there’s an ongoing
study of vasopressin for autism that, I guess the FDA thought
it was worth going back and trying again, suggesting maybe that it made a difference. We just finished a study
at the Oak Hill School of sulforaphane, which is a concentrated broccoli sprout extract that
was developed for treating oxidative stress in cancer. It seemed to have an effect
on heat shock protein and a kind of, thoughtful, physician, thought about heat shock and
kids with autism who tend to do better with fever
and he thought maybe sulforaphane could make a
difference for these kids. Did a randomized control
trial and active separated from placebo. We did the study at the Oak Hill school. Used metabolomics as a
biomarker of outcome. The study showed eight
out of seven kids got significantly better, but
it was an open-label trial and we’re now just analyzing
our metabolomic data. And again, oxytocin showing a difference. I’m near my last slide, so, there are things that suggest
mitochondrial function might make a difference,
giving Co-Q10, no good studies showing that benefit. Medical marijuana, not good
studies but I’d have to say I have maybe 20 kids that I’ve tried on first medical marijuana,
then THC and CBD, together, or first separately and then together. I don’t think it’s a miracle drug. You maybe saw the article
in the New York Times, there’ve been one in Atlantic
Monthly, several others. I think it makes a difference
for some kids where I’ve tried absolutely everything and it seems to work. I have one family where I’m sure it’s the
grandfather that’s taking the medical marijuana and (laughing) (audience laughter) he says his kid’s doing a lot,
his grandkid’s doing a lot better (audience laughter) but, you know, I reviewed
a grant awhile ago that was looking at the endocannabinoid system and treating people with with cannaboi- cannabidiol and I thought that was the
craziest idea I’d ever heard of and now it’s becoming something
seriously talked about in terms of things that
might make a difference. Looking at other things
like GABA-A and vitamins and minerals, I would
encourage you to think about doing everything that you
can to help these kids. The medical workup that
you heard about earlier. Speech and OT, behavioral,
treating associated symptoms with pharmacology, but thinking
about things like melatonin, Omega-3, vitamin D3, probiotics,
and digestive enzymes that can make a difference. For those of you who’ve known
me for awhile, you’ll know this slide because I show it at the end. It was we did an art contest
at the MIND Institute and we selected about 75 things that were shown. This is from a boy who
actually lives in Marin and I continue to see even
though he’s a young man now. But his mom said that he would always he would show an uncomfortable
situation and this, this piece is called The Haircut. You can see how he’s feeling
about getting a haircut and that bee is probably
the buzz of a razor. But she said when he had
an uncomfortable situation he always showed a way out,
and you can see the door on the side there. That was his way out. I hope that by our shifting our thinking, and thinking about ways to
help the body be more resilient and work and function
better, we might have kids, help kids with autism
find a way out of the sometimes challenging
disorder that they’re in. Thank you. (audience applause)

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