And Safe Upper Levels: Solid Science Versus Bureaucratic Bias
5 March 2001
by Wyn Snow, Managing Editor
the national Institute of Medicine (IoM) has cautioned that overdosing
on vitamin A can cause birth defects and liver damage. Down similar
lines, a letter published in the British journal Nature
warns that taking 500 mg of vitamin C daily might be harmful. Other
stories about potential dangers of excessive vitamin and mineral
intake appear regularly in the media.
other nutrition experts and numerous supplement producers say most
supplements are safe. Indeed, Dr. Adrianne Bendich (coeditor of
three books and two Annals of the New York Academy of Sciences and
chapters in other technical books, as well as author and coauthor
of more than 75 scientific articles on vitamin biochemistry and
safety) performed in-depth analyses of more than 50 years of literature
on the safety of five vitamins (including vitamins A and C) -- and
notes in an interview in Whole Foods Magazine, "It
is remarkable to find that almost all of the safety issues often
mentioned are not based on solid data."
the other end of the scale, the Institute of Medicine (IoM) also
says most Americans get enough vitamins and minerals from their
food (with a few exceptions such as calcium and folate) -- yet nutrition
experts told participants at a conference held at the Children's
Hospital Oakland Research Institute last June 2000 that many Americans
with the lowest income do not get enough vitamins. Bruce Ames of
the University of California at Berkeley says, "Wherever you turn
around . . . the poor are eating such poor diets I think they are
battering their DNA, causing cancer and maybe damaging their brains."
such disparate opinions being voiced by experts, how do consumers
decide what to do? Should we simply eat more fruits and vegetables?
Take a multivitamin "just in case" our diets don't provide enough?
And what about those "mega" doses of vitamins and minerals that
some people take to optimize their health? With almost half of all
Americans taking supplements of one kind or another, such questions
pose serious public health concerns.
guidelines from Institute of Medicine
national Institute of Medicine (IoM) recently issued new dietary
guidelines -- covering Recommended Dietary Allowances (RDAs) and
safe upper levels -- for two vitamins and several minerals. It is
the fourth in a series of reports beginning in 1997 that have changed
the RDA landscape into an alphabet soup of "dietary reference intakes."
If EARs, RDAs, AIs and ULs are unfamiliar and confusing, you are
not alone when it comes to understanding nutritional terminology
(see sidebar explaining
do these new dietary guidelines mean? Are they reliable, objective,
useful and comprehensive? Are they solid science or partisan social
policy? Reconciling complex and sometimes contradictory "standards"
can be perplexing and even a health hazard. Just as importantly,
non-critical acceptance of supposedly objective science can have
far-reaching consequences in terms of health policy and legislation.
SupplementQuality.com asked several experts for comments on these
issues while placing a magnifying glass on some of the fine print
in four lengthy reports issued to date. Some of our findings are
both surprising and controversial. We discussed our concerns with
Professor Robert Reynolds, a world-renowned researcher at the University
of Illinois at Chicago, who says, "RDAs and safe upper levels are
more political than scientific." (See our interview
plenty of guesswork
might think that RDAs represent clearly defined values, derived
from extensive scientific data, that say how much of a nutrient
you need to maintain optimal health. But our source at the Institute
of Medicine (IoM), acknowledged that "There's still a lot of guesswork
are actually estimates, based on surprisingly limited studies, often
involving small numbers of people and incomplete data. Essentially,
the IoM does the best it can with sketchy evidence to establish
either a recommended dietary allowance (RDA) or an adequate
intake (AI) level.
as identifying a fingerprint depends on being able to see enough
of the lines and whorls, establishing an accurate RDA depends on
having enough data to extrapolate from a small number of people
to the overall population. In assessing the evidence, we reviewed
parts of several lengthy IoM reports in an attempt to judge the
completeness of the evidence.
how complete is the evidence?
began with thiamin (vitamin B1), the first vitamin to be isolated
in pure form (1926), thinking there would be ample underlying research.
We discovered that the RDAs for thiamin are based on 9 studies of
105 people. Surprised to find what we thought was a rather small
number of people, we contacted the IoM to see if these limited studies
were accurate and typical.
Trumbo, Senior Program Officer of IoM's Food & Nutrition Board,
says, "Some of the RDAs are based on smaller samples. However, research
indicates that for the most part, human metabolism varies within
a fairly narrow range -- so that 97% of the population falls within
20% of the peak of the bell-curve distribution. Most vitamins are
enzyme cofactors, so the body's use of them is closely tied to metabolism."
(See sidebar for explanation of enzyme
cofactors, vitamins, minerals, and metabolism.)
the IoM first determines if the data provide enough detail about
a nutrient to determine an estimated average requirement (EAR):
the daily intake that meets the nutritional needs of 50% of the
people involved in the study and presumably in the population at
large. If so, this establishes a central peak for the bell-curve
distribution -- and statistical methods can then be used to calculate
an RDA. But if an EAR cannot be determined from the data for
a nutrient, the IoM develops an adequate intake (AI) level, which
is also an estimate. (See sidebar for explanation of bell-curve
distribution and how the RDA and AI are calculated).
persistent difficulty the IoM faces is that data may be plentiful
for one age group or gender, but sparse for another. In other words,
as you may have observed yourself, it's important to adjust intake
levels for age, gender and activity factors, as well as individual
issues. The IoM, faced with such unknowns, extrapolates -- using
data from one gender or age group as the basis for the RDA or AI
for another. In the reports we reviewed, the chapter for each nutrient
ends with a section describing additional research the IoM feels
would be valuable. A significant fraction of their recommendations
deal with filling the gaps in currently available data. (See sidebar's
from the IoM reports for calcium and vitamins C, D, and
another thing about RDAs and AIs you may have missed: they're designed
to prevent classical deficiency diseases rather than to optimize
health. The original RDAs were developed in the 1940s by the military
as a dietary guideline for US combatants in World War II. In the
years since, they have been expanded to address the needs of women,
infants, children and older people as well as young men; responsibility
for establishing RDAs moved from the military to the National Academy
of Sciences and its Institute of Medicine (IoM). From the beginning,
however, RDAs were designed quite literally as the smallest amount
of a nutrient that will prevent 97% of the population from becoming
ill with scurvy (vitamin C), beriberi (vitamin B1), rickets (vitamin
D), and other identified deficiency diseases.
thing few Americans realize: the new RDAs won't appear on supplement
labels until the IoM completes its fifth report, expected later
this year. Until then, labels still use information from the previous
set of RDAs published in 1989.
IoM's new RDAs are beginning to address wider health concerns: for
example, the criterion used to establish an EAR for vitamin C is
related to its antioxidant properties, and the new RDA is higher
than the previous one (now 75 mg for women, 90 mg for men). However,
the IoM chose criteria for vitamin E that are "based largely on
induced vitamin E deficiencies." Even though the IoM says, "A large
and growing body of experimental evidence suggests that high intakes
of vitamin E may lower the risk of some chronic diseases," it then
characterizes this research as "limited and discordant" and therefore
not solid evidence for recommending higher vitamin E intakes.
IoM takes a conservative stance in deciding whether new research
has conclusively proven the value of a nutrient in relation to a
disease. However, two other factors also contribute to the IoM's
tendency to keep RDAs low.
IoM have it right?
developing an RDA, IoM committee members use a traditional peer
review process. First, they decide which criteria to use as a measure
of adequate intake -- such as blood levels or urine excretion of
a vitamin compound. Next, they select the scientific literature
relevant to that criterion and weigh the studies based on the usefulness
and relevance of the experimental design. Finally, they discuss
their disagreements and reach consensus based on the evidence. However,
a closer scrutiny of the IoM's membership and interests uncovers
two important sources of potential bias.
Jonathan Wright, a well known alternative-health practitioner and
author whose past conflicts with the FDA have made him a controversial
figure, notes an obvious, but little commented-on fact: members
of the IoM all espouse a traditional point of view. "They're all
coming from the same side of the fence," Dr. Wright says. "No one
is looking at what might be called the natural medicine point of
Wright also states the IoM gives little weight to research that
doesn't agree with their preconceptions and gives this example:
years ago in the American Journal of Clinical Nutrition
(which is regarded as the leading publication in the field), a
research team reviewed the safe upper levels of vitamin D. The
team's analysis looked first at the view that our bodies have
evolved to take a full day's worth of sunshine, then examined
the scientific literature. Both supported the notion that the
safe upper level of vitamin D is 10,000 IU, making 2,000 IU five-fold
too low. The Journal did not present any editorial opposition
to this notion, which they often do when they disagree with an
author's conclusions. Yet, where has the Institute of Medicine
set the safe upper level? It's so far out of touch."
month's issue (volume 73) of the American Journal of Clinical
Nutrition contains another article about vitamin D by these
same authors describing their research with 61 people. Vieth, Chan
and MacFarlane state that a 100 mcg (4,000 IU) daily dosage of vitamin
D3 "effectively increases blood levels of [vitamin D] to high normal
concentrations in practically all adults, and [serum levels] remained
within the physiological range; therefore we consider 100 mcg to
be a safe intake."
comparison, the IoM chose serum calcium rather than serum vitamin
D as their criterion for setting a safe upper level (UL). They set
the UL at 50 mcg (2,000 IU), even though they viewed 60 mcg as the
largest dosage having no negative side effects and 95 mcg as the
smallest dose in their literature that had caused a rise in serum
calcium above the level they characterized as normal.
information about safe upper levels and how they are calculated
appears later in this article.)
funding: Another bias?
Julian Whitaker, author of eight books on nutrition and health,
points out that the packaged food industry has a vested interest
in keeping RDAs low. This same industry funds much of the nutrition
research in the US and more than a few academic professorships,
a fact that Whitaker suggests further clouds research objectivity.
to Dr. Whitaker, "When RDAs are low, it's easy for a juice manufacturer
to put 60 mg of vitamin C into a glassful of their product and claim
it contains 100 percent of the daily requirement. But if RDAs are
set at higher levels, such as 500 or 1000 mg of vitamin C, amounts
that many people take to prevent catching cold, then 60 mg of vitamin
C in that glass would be a mere 12 or even 6 percent of the RDA,
which is a much weaker claim."
Wright and Whitaker's point of view, the composition of the IoM
could be improved by including more points of view among its members,
and its conclusions would be stronger if nutrition research was
funded by more objective sources. Much university research is funded
by food companies, a topic that deserves review in its own right.
A third concern deals with how we determine the "normal levels"
of various nutrients in the body.
"normal" is normal?
nutrition -- just as in other scientific research -- the quality
of data sources is crucial to the value of the results.
Dr. Wright points out, the term normal in statistics means
the average. He observes, "Normal blood levels were drawn up some
years ago by taking blood samples from a group of people and drawing
the usual bell-shaped curve. That's great if you're working with
a population that's eating enough of the nutrient, such as 100 organic
farmers eating their own produce, versus 100 junk food junkies.
[Between the two] you'll get vastly different 'normal' levels. The
word normal is used differently in statistics where it means
average, and in everyday usage where it means healthy."
early nutritional studies of RDA needs were flawed by the fact that
they used institutionalized populations -- such as incarcerated
prisoners and individuals suffering from congenital retardation,
whose dietary intakes could best be described as low-cost and
limited, and whose metabolic needs may differ in important ways
from the wider population.
high levels of chronic diseases (heart disease, stroke, cancer,
diabetes) and excessive intakes of fat and sugar associated with
the fast food diets consumed by many Americans combine to suggest
that "normal" is a problematic concept at best. We need to be aware
that the data characterizing normal levels may be limited,
laced with conjecture and experimental flaws. Individual differences
-- long accepted in education as a critical factor in tailoring
pedagogical methods to the needs of each student -- occur in human
physiology as well, and are not addressed by the RDA's "one size
fits all" philosophy.
science, RDAs do not have the robust character and solid underpinnings
we might want in order to view them as substantive and reliable.
However, RDAs do provide a useful estimate of a minimum intake amount;
getting less than this amount probably puts one's health at risk.
But what about maximum amounts? How accurate are the IoM's safe
upper intake levels?
upper levels - Do no harm!
In establishing a tolerable upper intake level (UL) for
a nutrient, the IoM's goal is to ensure that supplement consumers
experience no adverse events (negative side effects) from taking . . .