Dietary Supplement Practicum (20 of 21): Analysis of the Evidence

>>Becky Costello:
And our last speaker, but not least,
today, is Paul Thomas, who’s a scientific
consultant with the office also. And he works primarily preparing the dietary
supplement fact sheets, along with other
educational materials, and does a lot
of interaction with the media. And Dr. Thomas
also manages the Federal
Working Group on Dietary Supplements, so that’s our
federal partners that have interest
in this area. And it serves as a mean
of communication between ODS
and the federal partners to co-fund research and expand opportunities in terms of research
investigator training, and strength and collaborations
throughout. So, please,
welcome Dr. Thomas. [applause]>>Paul Thomas: Thank you,
good morning. I’m going to give you
a few examples of research
on supplements for the
different reasons that people
take supplements; research that’s good,
not as good, and simply what
we’ve got to date. And I’ll conclude
with some lessons that I take away,
at least, from this practicum
as we study supplements, as we use them
ourselves, and as we recommend
them to others. So, Dr. Dwyer
told you earlier about why people
take supplements. And there are three
broad reasons, I think. First, what some might
call nutritional insurance. You don’t eat as well as
you should all the time, and you think you may
not be getting recommended amounts of all
the nutrients. And then there are
certain groups that are advised
to get nutrients from either
dietary supplements or fortified foods, like folic acid before
and during pregnancy, and people over
50 for B12. And then some people
supplement because they hope
for some kind of benefit in a general way, just kind of to feel
better than they do or to have their body
work better, like an immune system that might help
prevent colds and flu. And down the line, over use for many years
and decades, maybe to be more
resistant to diseases like cancer
and arthritis. And then some
people supplement for very specific
targeted purposes. An athlete might take
an ergogenic aid to enhance performance; maybe just for stronger
nails, fingernails. And people take
supplements to manage their diseases and health problems,
of course. Now, supplements,
of course, can’t be promoted
for disease prevention or treatment, but people can take them
and health professionals can recommend them
for these purposes. Now, Dr. Regan Bailey’s
research shows us that people
take supplements mainly to improve or maintain
their health. You’ve heard this
from several speakers. They want results. They’re not taking them
nearly as much just to supplement
their diets. And I’ll give you
research examples for each of these
three broad reasons. So, let me start
with the multi. Again, but I’m going
to go somewhere different with this. A supplement of only or mainly vitamins
and minerals. They’re the most
common supplements used in
the United States as you’ve heard by far. And some one-third
of all Americans take multis and they count
for about one out of every six dollars
spent on supplements, or over $6 billion
a year. Now, the multi is arguably the
product to supplement the diet for nutritional
insurance — an easy and inexpensive
way to meet or even exceed recommended
nutrient intakes, right? But there’s no standard
or regulatory definition for a multi, like what nutrients
it has to have and at what levels or if it might include
other ingredients, like herbs. Companies choose
the types and amounts of
the ingredients in their products. So, the result is that there are hundreds
of multis in the market, none of them
completely alike. Many claim to be
complete and balanced, which you would want for
a nutritional insurance. But are they? So, here’s a nutrient
breakdown of two of the bestselling
all-in-one multis for senior men,
50 and older. Now, this chart
is hard to read, but just focus for
a second on the colors. The nutrients in blue have the greatest
differences in amounts between the two products
of 100 percent or more of
the daily value. Now, when yellow
is where the nutrients are pretty high, more than 150 percent
of the DV. And green is where
the nutrients are much lower, less than 50 percent
of the DV. And DVs, of course, are simplified versions
of the RDAs and AIs. So, this is easier
to read, just the nutrients
with the colors. So, these two top
selling multis are quite different
from each other. For example, one is three times
higher in Vitamin K, but the other
is three times higher in chromium
and thiamine. And all that yellow, three times
the DV for B6, more than four to
16 times the DV for B12, more than twice
the DV for manganese, of all things. Selenium, above 150 percent
of the DV in one, but below 50 percent
in the other. And then there’s
the green, where the nutrients
are low. Mostly calcium,
magnesium, especially potassium, where the amounts
needed, you know, in hundreds or thousands
of milligrams, are high. Adding the DV
of these nutrients would make the pill
too large to swallow, of course. Now, some multis
come as daily packets of several pills. Their advantage
is mainly that they provide more calcium
and magnesium, but almost all multis,
even in the packs, are very
low in magnesium — in potassium. My point is that taking
a multi for nutritional insurance is like buying a policy
full of coverage gaps and excessive add-ons. And that’s the case
for multis for seniors, younger men and women,
and even kids. Well, so what might
a better one look like? Well, one option might
be to include nutrients at consistent fractions
of the DV, say, 25 percent for people
who eat really well, and 75 percent
for really poor eaters. And then why do multis
provide so many nutrients at or above the DV if it’s meant
to be a supplement and not a substitute? Even a terrible diet
provides some vitamins and minerals. And another option
would be for the multis to emphasize more
the nutrients of concern in the American diet as noted in the latest
dietary guidelines for Americans. Vitamins A, C, D, E, K,
calcium, magnesium, potassium, choline, which isn’t even in
any of my two examples. And not be
so overgenerous with most of the B
vitamins and include
more potassium, which will be one
of the four nutrients required on the new food and supplement labels
next year, that is, if
they’re not delayed. Well, anyway, beyond
nutritional adequacy, supplements are also
used in the hopes of reducing
chronic disease risk over time,
including the multi. And you heard about the
Physicians Health Study, too, yesterday
from Dr. Sesso. It examined whether
taking a multi could keep subjects
healthier for longer. It really was
an elegant study and it had quite
a simple design. Starting in 1997, almost 15,000 male
doctors across the U.S. were randomized
to take either a daily Centrum Silver or a placebo
for about 11 years. They were middle aged or
older and mostly white. And Centrum is
the best-selling multi on the market. Now to prevent
heart disease, the multi was
of no value. And it didn’t matter
whether the subjects had any history
of heart disease or what their baseline
nutritional status was. Also, the multi
didn’t slow down or prevent
cognitive decline and it didn’t prevent
age-related macular degeneration
of the eyes either. But the results
were better for cancer. Men taking the Centrum had a lower risk
of cancer. It was about
eight percent less and given a hazard
ratio of 0.92. And the researchers
called this apparent benefit modest. That’s their word. And yet, there were
no differences between the groups for
site-specific cancers like the prostate
or the colon. And cancer mortality was
the same in both groups. And the multi also modestly
reduced cataracts. Of the 1,800 cases
that developed, there were 73 fewer
in the men taking the Centrum
compared to the placebo. Now, one good thing
the investigators did was to use a version
of Centrum Silver that stayed exactly the
same over the 11 years. The dozens
of ingredients and their amounts
didn’t change over time, as they do for multis
in the marketplace. Today’s Centrum Silver,
for example, has more Vitamin D, has less A,
more of the A in the form of beta
-carotene than retinol. And it has the added
carotenoids, lutein and xanthene. Whether these changes
would affect the results of the study really
is anyone’s guess. And of course,
we don’t know whether these results
apply to women or to people who take
a multi at earlier ages or for a longer time. And would the results
even apply to a more diverse group of middle-aged men that aren’t as
well off as doctors and might not take as
good care of themselves? And since most subjects
were white Caucasians, would they even apply
to other racial and ethnic groups? So, on the basis
of this study, would you take
or recommend a multi hoping that
it might increase a healthy lifespan? Well, given the
modest benefits, there are clearly
more important things you can do
to reduce your risk of cancer
and cataracts. And when the U.S.
Preventative Services Task Force looked at all
the studies on multis and disease risk, they concluded that the
evidence is insufficient to determine the balance
of benefits and harms for the prevention of cardiovascular
disease or cancer. And they, of course,
called for further research. We always do that. One bottom line is that when you read
a study on multis, you need to know
how they were defined. Many speakers
have mentioned that or in doing your
own research on them, choose an option
or define them yourself, and know what supplement
products would be included or excluded by your arbitrary
definition. So, let me discuss
another clinical trial with ingredients
found in supplements, this time
for disease treatment, and specifically
for age-related macular degeneration. It’s a leading cause
of blindness in the elderly. And over time,
blind spots develop in your center of vision and your vision
gets blurry. Now, these two
are elegant trials, but they have a much
more complicated set up. In the first study known
as the Age-related Eye Disease Study, or AREDS, 3,640 adults,
55-80 with some AMD or evidence
of developing it were randomized
in four groups. One group took a daily
antioxidant combo of 500 milligrams
of Vitamin C, 400 IUs of E, and 15 milligrams
of beta carotene. Another took a high dose
of zinc, 80 milligrams and because
that was so high, some copper
to balance it. And that’s because
an earlier small study found that high doses of zinc
might help vision, that’s why
they included it. A third group
took the antioxidants plus the zinc
and the copper and the fourth group
got the placebo. Now, obviously
this was a disease treatment study, but it has a prevention
aspect too, maybe slowing
the progression of early or intermediate AMD to its more
advanced forms. It turned out
that those who took all the five ingredients benefitted the most. Using the combination
every day over five years cut the risk of those
with intermediate AMD getting advanced
AMD by 25 percent. Alas, the supplements
didn’t reduce progression from early to intermediate AMD. Now, after this study, all the interested
subjects were allowed to take
the full combo and they were followed
for an additional five years. And again,
the risk of progressing from intermediate
to advanced AMD was reduced
by 27 percent. Now, by the way, I doubt
anyone would call this antioxidant
combo a multi. It’s certainly not used
for nutrition adequacy, but by some definitions,
it is. It has five vitamins and
minerals and no herbs. Well then,
there was AREDS two. The AREDS one formula
was tweaked to see if it might help
more people. First, they removed
the beta-carotene since two earlier trials showed that high doses increased the risk of
lung cancer in smokers. And it was replaced with
two other carotenoids, lutein and zeaxanthin which are actually found
in the macula of the eye while
beta-carotene isn’t. There’s a lot
of these carotenoids in green leafy
vegetables, and AREDS1 found
a relation between eating
these foods and a lower risk of AMD. Now, also, they reduced
the — the amount of zinc. In AREDS1, those who
took the high zinc dose, they were hospitalized
more often for urinary
tract infections. Also, the men developed
an enlarged prostate more often, and women were more
likely to get stress incontinence. That’s, like,
leaking urine when you cough
or you laugh. And then they added
the fatty acids, EPA and DHA. In AREDS1,
subjects who ate fish just two times a week had a lower risk
of intermediate and advanced AMD, so can we bottle that? So, in 2006,
AREDS2 began. It had 4,200 subjects
with intermediate AMD in both eyes
or intermediate in one and advanced
in the other. And they were the same
age range as in AREDS1, 50-85, and they were treated
at 82 clinical centers across
the United States. The subjects
were randomized into four groups. Now, one took
the AREDS formula with the zinc
and the beta-carotene, which was now serving
as the control. Another group took AREDS with 10 milligrams
of lutein and two of zeaxanthin. And a third group
took AREDS with one gram
of DHA and EPA, and a fourth group
just took it all. Now, here’s where
it gets complicated because in these groups, subjects were
also randomized so that the AREDS formula
had some — of some had
beta-carotene removed including
in all the smokers. And in others, the zinc
was reduced from 80 to 25 milligrams. Now, the main findings
were that the
lutein and zeaxanthin — yes, easy for you
to say — zeaxanthin and omega 3s gave no added benefit to
the basic AREDS formula. They didn’t further
reduce AMD progression, but there were
lots of subgroup analyses and results, and here’s just
a few of them, the gist. While the original
AREDS formula can significantly
slow the progression from intermediate
to advanced AMD, a formula
with no beta-carotene and only 25 milligrams
of zinc works fine. And substituting lutein
and zeaxanthin for the beta-carotene seems
to improve the formula, but only in those people who don’t get much of these carotenoids
from food. And there was
one important caution. It was
the former smokers who took the AREDS
formula with beta-carotene had twice the amount
of lung cancer compared to those taking
the formula without it. So, it’s not just
current smokers who are at risk. So, the AREDS studies
really are a great example of where good science, including evidence
of efficacy and safety, you know, can and should be used to drive
clinical practice. And two years ago, the American Academy
of Ophthalmology told its members
to consider using the AREDS formulas to treat patients with intermediate
or advanced AMD. But they weren’t
appropriate for those with early AMD. But the reality here is
that for many supplement ingredients
or combinations, there’s either
no good research or what’s available
is really just a jumble of studies
of variable quality, no consistent bottom
line of value or safety, and no reputable expert
body would weigh in or give the therapy
a thumbs up. So, let me give you
two examples. This is the B
vitamin biotin. It’s an ingredient
in supplements that are touted
for improving nails, hair, and skin. Our office was asked
about biotin’s value in strengthening nails
a couple of months ago, so we looked at
the published research. What it amounts to are
three small studies with one in German, with only an abstract
in English. A total of 102 patients
with brittle, splitting or soft nails. They were treated
for five to 15 months with a very high dose
of biotin, two and a half
milligrams per day or more than eight times
the current daily value. And the supplement
appears to improve nail hardness
and thickness in a majority of this
small group of patients, but not in others. And the studies can’t
tell us who might or might not benefit. And my other example
is sodium bicarbonate, baking soda. It’s actually available
as a dietary supplement. And it’s taken
by some athletes to improve
their performance. Now, this is
a supplement that literally
has been studied for about 80 years and there are dozens
of studies in swimmers, in cyclists, in rugby
players and the like. But most of the studies
include only a dozen or so subjects, they’re tested in a lab
over several days in rather
artificial conditions. And they show that
people have different responses to the bicarbonate
loading. Some seem to improve
their performance in strenuous exercise over several minutes
or in sports that have intermittent
levels of intense — high intensity activity. And then,
there are others who get no benefit. And in some,
the supplement actually hinders
their performance. And in any
given individual, the supplement can
help it one time, but not in another. And despite all this
work, we don’t know why. We’re not even sure
about high — how bicarbonate might
help performance. The current thought
is that it reduces a metabolic acidosis from lactic acid
build up that
makes you feel tired. You know, so what to do
in both these cases? I can understand
those who might say not to bother
with the supplements because the research
support is weak or not conclusive. But I can
also understand those who think
it’s worth experimenting to see if the supplement
works for them. Especially if there
seems to be little or no risk
of side effects. Biotin, for example, seems quite safe
in even high doses and no upper safety
level has been set. And so, that’s the case
with using many supplements for reasons that go beyond
nutritional insurance; a little information or
conflicting information about possible benefits and virtually
none of the studies are powered enough to
uncover potential harms. So, depending
on our attitudes about supplements, our ideology,
our worldview, as a user
or as a practitioner, we’re likely to pretty
much avoid them or to see them
as complimentary or integrative
approaches to address
health matters. Now, you’ve learned
that there are all sorts of challenges
and considerations in researching
dietary supplements. And that’s just
for the hundreds, if not thousands,
of single ingredients. The bulk of the science, the challenges multiple for
ingredient combinations. But — and the products
being brought to market are increasingly
combinations of ingredients touted
for specific purposes. They’re called,
again, specific condition-specific
supplements for reasons like heart
and bone health and blood sugar control
or weight loss. And they fit into why
a majority of people say
they take supplements — to improve or to
maintain their health. Now, take joint
health for example, a category with more
than $1.6 billion a year in sales. And on the right
of this slide, I’ve listed just
a small number of the ingredients that
might be found in them. Each company’s entries
have a different mix of ingredients
and amounts. You know,
the thinking behind many of these products seems to be
to combine ingredients that have even the
tiniest bit of science behind them of benefit
in the hope that one or more of the
ingredients in them might help the user. Or even better, maybe there’s
some ingredient synergy. But without
any research support of the combination, of course,
you can’t know. And just maybe, the combination
might not work as well as single
ingredients or that any synergy
might actually work in the other direction of no benefit or increasing
the risk of harm. The user becomes
the research subject. Now, the focus
on condition-specific supplements and both — with both single and
combination ingredients is evident on both
company websites and in the
physical stores. You can search online
for the body part or the system you want
to fix or maintain or for a problem area, for your liver,
for your urinary system, or for something like
pain or insomnia relief, there are sections in
stores for supplements for cleaning
and detoxification, for heart health,
for healthy aging. I like to tell the story
of when I was working in the health food
stores in the 1970s, the supplements
were organized in alphabetical order, you know, Vita
A to K to Z; the minerals, you know,
all the way down to zinc and herbs
alphabetically. That is no longer the
case in the marketplace. Now, obviously, we need
more, or in many cases, really just
some research on these products
to evaluate their value and their safety
as more people use them. But their number
and composition in the market grows so much faster than
the pace of our science. The industry refers
to this as product innovation and the need
to be innovative. So, we as investigators
probably need to talk more about the kinds
of research we need and which supplements, which supplement
ingredients, and combinations
to study. So, let me wind
down here. Over the three days
of this practicum, you’ve learned a lot
about dietary supplement efficacy,
safety and quality, and oversight
and regulation of the industry. And I — as I’ve
listened to these talks, this time and in
previous practicums, these are some
of the lessons that I take with me about choosing
and using supplements. The first is to choose
the right dose and timing regimen.
Often, we have reasonable
science to guide us. Like the doses of
glucosamine and chondroitin most often used for
treating osteoarthritis are 1,500
and 1,200 milligrams per day respectively, but taken as two
or three doses separated
by several hours, not all at once. For St. John’s Wort
to treat mild to moderate depression, the usual dose is
900 milligrams per day taken in three
equal doses spaced out of
300 milligrams. And for
maximum absorption, keep your calcium intake at any one time
to under 500 milligrams. Second, consider
the supplement form. And for some
ingredients, this is important. Again, with calcium,
calcium carbonate is best absorbed
with meals, but calcium citrate
can be taken anytime. For chondroitin,
which is a carbohydrate polymer, one of low
molecular weight might be best absorbed. And often,
we don’t really know. With echinacea,
for example, you have your choice of
three different species; angustifolia, pallida,
and purpurea. And four different
plant parts; the roots, the stems, the leaves
and the flowers. And then combinations
of species and parts in all different kinds of echinacea
supplements. Which is best? You can’t really know,
but for what it’s worth, Consumer Lab advises that the aerial parts,
the stems, the leaves, and the flowers
of purpurea. So, if you’re
going to try it, maybe that’s the one
to try first. A third consideration
is really mainly for botanicals. It’s often best
to choose a product whose composition
is standardized, like the ones typically
used in clinical trials. Many studies of gingko,
for example, they use an extract
standardized to 24 percent
flavone glycosides and six percent
terpene lactones. And for salt palmetto, a product with 70 to 95 percent
free fatty acids. And fourth,
in some cases, a supplement from
a specific company might be good
to try first. And that’s because
the company has actually studied
the product or the amount, the form and
the standardization of its ingredients actually conformed to
those used in studies. Now, we don’t usually
plug specific products, but sometimes one brand has more science
behind it than another. And here are some
other takeaways. If you take a supplement
for some purpose and it doesn’t seem
to be working, before you give up
on it, try a different brand, a different form,
a different mix, a different something. The reason might be
a quality problem with that product. Maybe another one
processed and manufactured differently with
different excipients, a different
chemical matrix might be more effective. In general, I think, avoid products
with proprietary blends. If you don’t know
the exact amount of each of the ingredients
in the product, you can’t know whether
they’re present in meaningful amounts. And of course,
the instructions for use on a label is either often
not very helpful, or is really wrong for what you’re using
the product for. And every time you buy a
new bottle of a product you’re taking, check the
Supplement Facts Panel. Products, especially
with multiple ingredients,
change over time. Be sure it’s
still something that you want to use. And some buying advice
that makes some sense to me. First, maybe buy
from companies that are large enough to have a national
presence. They’re likely to pay
more attention to quality issues in
supplement manufacture because they have
more resources to do so and more to lose if their reputation
is questioned. And maybe buy
from companies that are members
of supplement trade associations
like CRN and APA. They have codes
of conduct and expectations
for the development, manufacture,
and marketing of a members’ products
and ingredients. And then, maybe, buy products that
have been evaluated by a responsible
third party, like the USP and NSF, which evaluate
not only products, but a company’s
manufacturing and quality
assurance facilities. Or, which tests products that are already
being sold, but they don’t test
company facilities. Companies and products that pass are listed
on their websites and the products
may even have a third-party logo
on their labels. And then finally,
I’d also make use of the ODS Dietary
Supplement Label Database to learn the choices
you have available for any type
of supplement. By doing this, it’s
really easier to find exactly what it is
you’re looking for. My gosh, and with plenty
of time left, I am done. So, I will try to
answer your questions. I know you want
to get out of here. But also, let me
ask you, before I — something — what are the most
important takeaways that you’ve learned here
about studying, choosing and using dietary
supplements and about their oversight
and regulation? So, thank you. [applause] Any questions I can try?
Yes?>>Male Speaker:
On one of your slides, you talked about
sodium bicarbonate. And one of the things
that has not been addressed
at this weekend or this week was
the thought today about alkalizing
your body and that sodium
bicarbonate was something to be used
every day to do that. Are there any
thoughts on that?>>Paul Thomas: No, I mean, that is
the current rationale for how it might
be effective, that it would reduce
or counter the lactic acid buildup that ultimately
leads to fatigue or one of the reasons
why you get fatigue when you’re doing high
intensity activities. It’s not exactly clear
that that’s the case. And again,
we don’t understand why it happens
in some people and not others even
when their pH actually, you know, goes up
a little bit or why it works some of
the time and not others. Again, 80 years
of research, lots and lots of
small studies. One of the things about
sodium bicarbonate, it’s really
very interesting because the dose
that they’re — one of the things
they’ve kind of keyed in on is the actual dose of the sodium
bicarbonate to use. And that is about three
to five teaspoons of baking soda. Now, think of this.
That is incredibly salty and it is pretty much
inedible by itself and even in water. So, it’s put in a number of different
kinds of drinks where you’re obviously
trying to mask this. It leads
to water retention in a fair number
of people. You know, it leads
to a bit of nausea, upset stomach,
in some cases, vomiting and so on. Again, it occurs
some of the time and not in others.
But, it’s — if you’re looking for
a performance advantage, it is one of
the supplements that a fair number
of athletes are trying, particularly in, say,
competitive athletics. Not necessarily for
the weekend warrior, but when your time
may be a second or a fraction
of a second in some kind of race
or event might make some
sort of a difference, are you willing
to try that and risk the potential
side effects or see if it works
for you that one time
for that one race when it might not
have the other time?>>Male Speaker:
As a follow up, there’s another thing that seems to be hitting
the marketplace is that to do this for, say, illness prevention, like cancer
and things like that. Any thoughts on that?>>Paul Thomas:
No. No, I don’t. And we, as an office
don’t really get into the use
of dietary supplements on the whole for actual
disease treatment, but mainly
in its prevention. Just with the sodium
bicarbonate example, in addition to
dietary supplements fact sheet
on weight loss, we have one on exercise
and sports supplements that will probably
be done and out, I would hope,
by sometime next month. And it’s going to be
large and extensive as the one we have
on weight loss. And it includes
sodium bicarbonate. Yes, Johanna
[phonetic sp]?>>Female Speaker:
Just to continue on the bicarb, I think Paul and I,
for our sins, have been reviewing
a lot of articles for a supplement
for an unnamed journal. And several of them have
been on beetroot juice. And some of them
are interesting but inconclusive.
Beetroot juice apparently has a lot
of bicarbonate. And some of
the clinical pharmacists and physicians
in the audience, if you do a lot of work
with renal patients, there’s a great deal
of interest in bicarb and the whole
issue of acid base balance with them. And also, I know Bess
Dawson-Hughes at Tufts, who’s done a lot
of work on bone, they’re very much
interested in using food sources of — of bicarbonate — well
it’s not bicarbonate, it’s basically affective
acid base balance. I think prunes and some other
things like that –>>Paul Thomas: Right, it’s
basically kind of an — Mediterranean diet
that is, overall, more alkalizing because of the selection
of the foods than a standard, you know, meat,
potatoes type of a diet. The other thing
about beetroot, which we also look at in our upcoming
performance fact sheet is that beets, beetroots,
beetroot juice is also a very
high source of nitrate for endothelial function and expanding the
arteries a little bit and maybe promoting
a little bit more oxygenation
to the tissues. Some interesting
science there, some decent science
and overall, it’s still
a little bit iffy. It’s sort of
in that area where you can’t really
say definitively. You can’t really say
whether or not it’s going
to work for you. In the end,
it amounts to, you know, what’s
your world view? What’s your attitude
towards supplements? What’s your need for a
performance enhancement? And are you willing
to try this and for how long? And at what dose
and for what activity? Yes?>>Female Speaker:
Thank you very much for your presentation. I think I’m about to ask
a rhetorical question [laughs]. Given what we’ve
learned so much about the lack
of evidence and the need
to do more research, I’m wondering if you see
the office’s role as serving
as a repository, for lack of
a better name, of endorsements or clinical practice
guidelines. So, I appreciated
the example today that you used with
macular degeneration and the American Academy
of Ophthalmology’s statement based on current
best evidence. So, I’m wondering,
do we see this evolving as a place where we can see
a state of the science?>>Paul Thomas:
How about let me ask you to save that question, or we will answer it when our little panel
comes up, because that I want
to have other people involved in trying
to answer. Are there any more
specific questions about my presentation before we move
to the panel?

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