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SQ:
In reading the new RDAs published by the national Institute
of Medicine, we saw that the RDA for thiamin is based on only
9 studies covering 105 people. Isn't this a rather small number
to be extrapolating to millions of Americans?
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A:
It's certainly smaller than the number we would want to
have in an ideal world. Basically, if 105 people in 9 studies
is all they have to work with, then that's the data they have
and that's the data they work with.
In
developing an RDA for a specific nutrient, the panel first sets
one or more criteria for judging the adequacy of that nutrient.
For example, they might say that a particular compound in the
blood is a good indicator -- or they might use urinary excretion.
Next they establish which cutoff levels are appropriate. Then
they look through the scientific literature to see which studies
apply to the criteria they have selected.
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I
like to use analogies -- and here's one for the situation in
nutrition research. If you have $20,000 to spend on a new car,
you buy a Chevy [or similarly priced car]. If you have $40,000,
you buy a Lexus -- and if you have $60,000, you buy a Mercedes.
The difficulty is that the government is providing the Chevy
level of funding, not the Mercedes. And while the Chevy will
get us from here to there, it doesn't provide the degree of
comfort or certainty that a Mercedes will. So yes, you wind
up with small study sizes and a lack of data for various parts
of the population.
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SQ:
Such as having little or no data about men's needs for calcium
or children's needs for vitamin C.
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A:
Exactly.
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You
think 105 people is a small number? Here's a really bad situation.
I haven't checked the newest RDAs to see if they've made any
progress, but the 1989 RDA for vitamin B6 in infants is based
on a single infant. And if you read the paper carefully, it
looks like that infant was born to an abnormal mother. But they
went and did an RDA anyway .
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SQ:
That's pretty astonishing. At least now, if they don't have
enough data to have an estimated average requirement, they don't
issue an RDA at all. Instead, they establish an estimated "adequate
intake" level (AI).
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A:
Yes -- but the key word there is estimated.
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Biotin
is another interesting case. The AI for biotin is based on the
level of biotin in human milk, extrapolated to adults based
on body weight. Basically, the IoM says,"We assume babies are
getting enough, and since we know how much is in human milk,
we will extrapolate on body weight."
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But
this is absurd on several levels. First, adults don't drink
human milk. Second, infants are growing at a phenomenal rate
and it's not just in quantity. All their organ systems are still
developing and maturing. Third, we know that the nutritional
needs of infants are different from those of adults.
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SQ:
How is it possible that the IoM makes decisions like this, and
then presents them to the public as solid science?
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A:
The RDAs and AIs are more political than scientific.
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Many IoM panel members come in with their own personal agenda
-- and since they generally know more about that particular
nutrient than other panel members, their own personal agenda
usually carries the day.
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In
deciding which criteria to use for determining adequacy, this
is where judgment comes into it. The more we learn about each
metabolite, it changes our perception of the validity of each
assessment tool -- such as blood serum and urinary excretion
of specific compounds.
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Take
vitamin B6, for example. For years, I was one of the advocates
of serum pyridoxal phosphate (PLP). If you looked at the blood,
this looked like a good indicator of adequate intake. But then
we started looking at not just normal people, but unusual circumstances
-- such as pregnancy and lactation and disease-related circumstances.
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What
happened on B6 started with pregnancy. We noticed that there
were groups of people who had abnormally low levels of this
PLP form of B6, but they showed no signs or symptoms of deficiency.
If we used that one PLP criterion that everyone was using at
the time, then these people should have been dead! And clearly
they were not.
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Upon
further investigation, we found that the run-of-the-mill enzyme,
alkaline phosphatase, that exists in everyone's blood plasma
has a major impact on the concentration of that form of the
vitamin. As the enzyme activity goes up, PLP is broken down
to pyridoxal and the concentration of PLP goes down. The pyridoxal
then goes into the cells in the body where it is reconverted
back into PLP.
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So
if we look only at the plasma concentration of this one form
of the vitamin as was done for 20 years, we get a false picture.
PLP goes down whenever people have slightly abnormal activities
of alkaline phosphatase, and that occurs in many disease states,
slightly high or slightly low. It also occurs as a normal consequence
of pregnancy, so people for years were saying that pregnant
women were deficient in the vitamin when in fact the women were
not.
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This
example shows we can use an assessment tool for 20 years with
complete confidence that we're looking at the accurate status
of an individual, and then one day we realize we're looking
at it wrong. So after we discovered this, I announced at a talk
that all of the work and conclusions based on plasma PLP need
to be thrown out and we need to start over again -- and I gave
the reasons for it.
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So
whenever you're using a single index as the criterion of adequacy,
it can go from being the gold standard to being the mud standard
in a single day.
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SQ:
That would explain one reason why some of the RDAs have changed
over the years -- that our scientific understanding of how vitamins
work is improving. For example, the RDA for vitamin C has increased
because they're considering its antioxidant functions as well
as prevention of scurvy.
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A:
A lot of that increase in the RDA for vitamin C is a result
of political pressure.
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The
IoM has always chosen to err on the side of conservatism in
the numbers. Seldom do you see dramatic increases. They are
generally decreases. In 1989, the RDA for vitamin B6 was 2.0
mg for men. The new RDA is 1.3 mg, and that drop is unjustified.
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SQ:
That could have serious consequences for public health, especially
because dieticians use RDAs in designing diets for large groups
of people. A different kind of public health concern involves
people taking too many vitamins instead of not getting enough.
To address this, the IoM has also established a new dietary
intake guide for tolerable upper intake levels (ULs).
What is your opinion about safe upper levels?
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A:
Safe upper levels are an interesting concept and a nice
addition that needs a lot of work. There is justifiable concern
for toxicity of nutrients. We do need rational upper level guidelines
-- but we're not there yet.
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England
was considering setting an upper dosage level of 10 mg for vitamin
B6 pills. I testified before Parliament that the USA's upper
level of 100 mg on B6 is also too low, but at least it is closer
to a rational level. After my testimony, they decided to table
the matter for further study.
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The
data upon which the upper limits are based is even more fragmentary
than the data upon which the RDAs and AIs are based. Unfortunately,
in many cases, there is a huge gap between the levels where
side effects have or have not been seen. In those cases, the
IoM can set an unrealistically low level for the UL, when in
fact levels substantially above that level may still be perfectly
safe.
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SQ:
For vitamin C, one study gave dosages of vitamin C starting
at 1 gm (1000 mg), then increased the dosage by 1 gm at each
"step" and began to see loose stools in some of the people at
3 and 4 gm. In other study, the dosages given were 1 gm, 5 gm,
and 10 gm -- and some of the people tolerated 10 gm without
any problems. Yet the upper intake level (UL) is set at 2 gm.
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A:
The upper level is calculated using an uncertainty factor.
These uncertainty factors are totally arbitrary and politicall.
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The
upper levels are based on NOAELs (no observed adverse effect
level) rather than on LOAELs (lowest observed adverse effect
level). In many cases, there can be a very wide range between
a dose that has been seen to cause an adverse effect (LOAEL)
and the highest dose that has never caused any adverse effect
(NOAEL).
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The
upper level is calculated by dividing the NOAEL [the dosage
level with no side effects] by an uncertainty factor, which
ranges from 1 to 5. It would be better if they had used the
LOAEL and then divided by the uncertainty factor. Instead they
took the safe route and divided an already safe dose by the
arbitrary uncertainty factor.
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Thus,
the ULs represent what should be a very safe dose even
if taken over a long time. The ULs should not be considered
to be the highest safe dose. That level will be well above the
UL for each particular nutrient.
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SQ:
What about the overall usefulness of RDAs? Do they appy to everyone?
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A:
No. Every semester, I teach 300 students an introductory
nutrition class. I begin by telling people on the right half
of the room to stand up. Then I tell them, "RDAs do not apply
to half the population. At any one moment, approximately 50
percent is unhealthy. Anything from the sniffles of a cold to
terminal cancer. RDAs by their own definition are only for healthy
people."
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Then
I tell another nine people to stand up. And I tell them, "RDAs
are actually for almost all healthy people, but it does leave
off the upper three percent of the healthy population. So RDAs
do not apply to you either."
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SQ:
But it's not that the RDAs for all the vitamins and minerals
don't apply to those 9 people, right? It's really that any of
those seated people are likely to have one or more nutrient
needs that the RDA doesn't cover.
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A:
It's worse than that. Do you smoke?
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SQ:
No.
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A:
Good -- we know it's unhealthy. So should we make a different
RDA for smokers? We do know there's a more rapid breakdown of
ascorbic acid [vitamin C] in smokers. There are many factors
in otherwise healthy people that can change their needs for
various nutrients.
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So
RDAs are not a very good way of figuring out what you need.
It's a very broad target. And don't forget that the RDAs are
set above what the body actually needs. What the RDAs
do provide is a recommended level of dietary intake,
not the level of intake that is needed by your body. Your needs
are almost always less than the RDA.
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There
are exceptions to this, and those occur mainly in the prevention
of chronic diseases. This would include higher than RDA intakes
of vitamin E for reduction of risk of heart attacks. While high
dosage intake of vitamin E is still very controversial, the
data are becoming overwhelmingly convincing that intakes of
this one vitamin at levels that are impossible to achieve
by the diet alone are beneficial.
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It
will take years, if not decades, for the RDAs to catch up with
the concept of prevention of some of the chronic diseases. The
committee members pay lip service to this concept, but then
they turn their collective backs on the data. Maybe someday . . . ?
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Reader
Challenges Our Facts -- Scientist Replies To Criticism
SupplementQuality.com
received criticism from a reader that this interview contains
inaccuracies. In particular, the reader said "the B6 level was
set using more than one baby." Read
Professor Reynolds' reply.
