And Safe Upper Levels: Solid Science Versus Bureaucratic Bias
upper levels - Do no harm!
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 a dosage higher
than the RDA or AI. Therefore, the UL is set lower than the smallest
amount of a nutrient that has caused no discomfort or health
problem to the most sensitive members of the population.
the dangers of taking too much of a nutrient include neurological
damage, liver toxicity, and similarly serious consequences, there
is a clear benefit to establishing a safe upper level. However,
some negative side effects that ULs are designed to prevent are
better described as inconvenient rather than serious,
and in some circumstances can even be described as beneficial!
events or useful treatment?
vitamin C, for example. The overall safety of vitamin C is very
well documented -- but high dosages can lead to loose stools. The
IoM set the UL for vitamin C at 2 gm (2000 mg) to avoid "osmotic
diarrhea and gastrointestinal disturbances." Yet Dr. Whitaker says,
"Many European doctors recommend high doses of vitamin C as a laxative
because it's so safe."
research into vitamin C safety indicates that some people can tolerate
as much as 10 gm without problems, although others experience gastrointestinal
side effects at 3 gm. The side-effect threshold for the most sensitive
members of the population seems to lie somewhere between 2 gm and
3 gm, but exactly where is not yet clear.
E is another nutrient with an excellent safety record. The UL for
vitamin E is set at 1000 mg (same as 1000 IU) "based on the adverse
effect of increased tendency to hemorrhage." In this case, people
with a history of blood clotting could benefit from this "adverse
effect" of vitamin E, especially if done in conjunction with visits
to a doctor and/or blood-chemistry lab.
a parallel vein, the UL for niacin is set at 35 mg to prevent flushing
of the skin (a temporary reddening). The level at which people experience
this flushing varies widely, from as low as 25 mg in especially
susceptible individuals to as high as 1000 mg. While niacin flushing
can also include unpleasant tingling and itching or even burning
sensations, the negative side effect here is primarily social embarrassment
rather than medical. As Dr. Wright points out, "Niacin flushing
has nothing to do with safety."
for some of the safest nutrients, ULs might be viewed more as "therapeutic
thresholds" for specific kinds of problems than as boundaries separating
safe from risky use. But what about other nutrients, where the danger
of serious health problems from exceeding ULs may be more serious?
upper levels: Erring on the side of caution
popular joke recounts the frustration of a fellow searching for
his lost keys under a streetlamp -- because that's where the light
is. Any rational person can point out a better starting place: the
place where the keys were last seen. In a similar vein, in its zeal
to ensure no harm comes to the public from ingesting excessive amounts
of nutrients, the IoM may be looking under the streetlamp instead
of more fruitful places.
are two kinds of data about adverse effects. One comes from experiments
in which no adverse effects were observed among people taking certain
levels of nutrients. These data are called: no observed adverse
effect level (NOAEL). A similar kind of data occurs in studies
where some people do experience adverse effects -- resulting in
a lowest observed adverse effect level (LOAEL). These are
the equivalent of where the subject of the joke last had his keys.
Now, let's move under the streetlamp.
than setting the UL at the same amount as the NOAEL (no adverse
effects), the IoM has embraced a risk assessment procedure and policy
designed to protect people from toxic chemicals in the environment.
The result is a set of ULs that are lower than NOAELs -- achieved
by something called an uncertainty factor, which is basically
a fancy term for "we don't know." (See sidebar for explanation of
factors and UL calculation.)
providing a safety cushion in the form of an uncertainty factor
may be laudable, what is "uncertainty" really all about?
factors not so sweet
makes an interesting example. Here, there are no reports of adverse
events from high dietary phosphorus intakes. The IoM states, "Essentially
all instances of dysfunction (and hence, all instances of hyperphosphatemia)
in humans occur for non-dietary reasons." In other words, people
who are ill.
the IoM then bases the UL on the "normal adult range for serum phosphorus,"
takes the NOAEL of 10.2 gm, chooses an uncertainty factor of 2.5
(remember, the uncertainty factor is a guess), and winds
up with a UL of 4.0 gm! Notably, that's less than half of the NOAEL,
the lower boundary amount previously established as showing no adverse
effect! With an RDA for phosphorus of 700 mg for adults, the UL
is 3300 mg higher than the RDA, and the NOAEL is an additional 6200
mg higher than the UL -- an additional 6200 mg for which there is
no evidence to characterize it as unsafe.
phosphorus may not be the best example -- it is amply available
throughout the food supply in the amounts people need -- similar
guesses and calculations are being made for all vitamins and minerals.
In many of those cases, the consequences may not be so benign.
safety" and nutrient availability
29 January 2001, ConsumerLab.com, a supplement testing organization
that publishes test results on the Web, announced the removal of
a glucosamine/chondroitin product from their "passed the test" list
because its manganese content was higher than the UL.
consequences of excessive manganese intake are serious neurological
problems, and the LOAEL (where manganese levels in the blood begin
to rise) is only 4 mg higher than the NOAEL (no adverse effects).
In this case, the UL is exactly the same as the NOAEL (11 mg), so
honoring the UL as an accurate "safe upper level" is probably a
wise precaution, especially for glucosamine/chondroitin, which is
a supplement that many people take daily to prevent or reverse deterioration
of joint cartilage caused by osteoarthritis.
who choose especially manganese-rich vegetables should probably
avoid taking any supplement that contains manganese. Also, only
some glucosamine/chondroitin products contain manganese, not all.)
if other testing organizations follow ConsumerLab.com's lead with
respect to manganese and apply the same policy to other nutrients,
this could apply economic pressures on manufacturers to keep dosage
amounts under the UL, even for nutrients where higher dosages have
demonstrated safety. While we can hope that testing organizations
and producers would not adopt such an indiscriminate policy, such
a scenario cannot be dismissed.
are many reasons for minimizing RDA levels which work to the disadvantage
of the consumer, not the least of which is the profit motive. Just
as some food manufacturers have a vested stake in keeping RDAs low,
so do supplement manufacturers and distributors who wish to build
a "price floor" under supplements.
or limited RDAs mean smaller dosages; price inflation leads to smaller
product volume. The combination of the two results in reduced purchasing
power and a slow but unremitting reduction in nutritional value.
The consumer loses on both counts.
impact of international "harmonization"
efforts to "harmonize" the US and European regulatory environments
could have an equally serious impact on the availability and accessibility
the Codex Alimentarius (a United Nations initiative covering both
food and supplements) and the TransAtlantic Business Dialogue (TABD)
are working to develop transnational guidelines for supplements.
At the Sixth TABD CEO Conference held November 2000 in Cincinnati
OH, the TABD established several "next step" goals, one of which
seeks to establish maximum levels for vitamin and mineral supplements
based on ULs:
and recommend methodologies for setting maximum levels for vitamin
and/or mineral food supplements on the basis of upper safe levels
of total intake for these nutrients and intakes from other sources.
The responsible regulatory bodies are encouraged to cooperate
and establish one set of figures for maximum levels for vitamins
and minerals in food supplements on both sides of the Atlantic."
potency levels of vitamin, mineral, and botanical products are sharply
lower in Europe. Indeed, Britain was recently considering passing
legislation that would limit dosages of vitamin B6 tablets to 10
mg. When Professor Reynolds testified before a Parliamentary hearing
that the IoM's safe upper level of 100 mg was closer to a more scientifically
accurate level, that governing body decided to table the matter
for further study.
and safe upper levels: Is there a better alternative?
no two people are alike, fingerprints and DNA evidence are highly
reliable ways to identify individuals. Similarly, variations in
metabolism are commonplace. The value of RDAs and ULs for any one
individual depends on where that person falls on the bell curve
for particular nutrients.
as RDAs provide a reasonably accurate minimum intake level 97 percent
of the time, 3 percent of the time, they don't. With more than two
dozen vitamins and important minerals, many people are likely to
have one or more nutrient needs that fall outside the bell curve.
Whitaker doesn't use RDAs in his practice because "RDAs are for
the average healthy person, and my patients are sick. RDAs clearly
have a beneficial use only for prevention of scurvy and other classic
deficiency diseases in healthy people. They don't cover people with
asked how he determines what dosage levels to recommend for each
patient, Dr. Whitaker replies, "There are thousands of pages of
information on the physiology and biological action of how the various
nutrients work in the body and what constitutes a therapeutic level
in the body. I use nutrients in a manner that has been demonstrated
to be useful."
for safe upper levels, Dr. Wright offers this observation:
safe upper levels just don't make sense. One of my patients was
seeing an ophthalmologist for recurring corneal ulcers. I put
her on vitamin A and we raised her dosage to 100,000 IU -- where
her corneas stopped ulcerating. Her ophthalmologist sent her to
an internist because he was appalled by this level of vitamin
A intake. Both doctors were sure it was toxic, so the internist
took blood tests -- which showed 'normal' levels of vitamin A.
The point is this woman needed an intake level ten times higher
than the UL to achieve 'normal' blood levels of this vitamin."
measures of nutritional adequacy
wise detective finds out whether a glove fits a suspect before pointing
an accusing finger. Instead of a "one size fits all" approach to
RDAs and ULs, Dr. Wright would like to see the development of what
he calls functional measures of nutritional adequacy. He
explains that for each nutrient, there are threshold symptoms both
for deficiency and for getting too much, and describes an example:
very easy to tell if someone has folate deficiency. One of the
common types of white blood cell is a neutrophil, which is made
in the bone marrow. If a person does not have enough folic acid
in their blood marrow, the neutrophils released are not mature
(and have 5 lobes). If the person has enough folic acid, the neutrophils
are fully mature (the lobes have consolidated into 3). So all
you have to do is look at someone's blood under a microscope.
It's easy to see, easy to count. Some people will have 100% mature
neutrophils on an average junk food diet. For some, it takes an
intake of 5,000 mcg/day -- and the RDA is 800 mcg."
Wright also gives examples of getting too much of a nutrient. He
explains, "Niacin toxicity is always signaled by nausea, when the
niacin is starting to overwhelm the liver. Vitamin A toxicity is
heralded by headaches, dry skin, cracked lips, pain in the long
bones. It makes much more sense to be aware of these early warning
signs of toxicity -- which are sensitive to individual needs and
individual responses. If you start getting symptoms, stop taking
the nutrient or reduce the dosage."
according to Dr. Wright, "One has to be super cautious about everything
during pregnancy. The developing fetus is very vulnerable and sensitive,
and it can't tell you if it's got a headache."
gray cells" and what works best
fans of the famous fictional detective Hercule Poirot know well,
the last exercise in any mystery is assembling all the suspects
in one room and then using one's "little gray cells" to determine
the mystery to be solved is how best to optimize health, both as
individuals and as a society. In this case, there are no culprits,
only competing experts and schools of thought as to what approach
long as we keep in mind that RDAs, AIs and ULs are conservative
estimates that are designed to cover the main area of the bell-curve
distribution, they provide useful information about a range of dosages
that are likely to keep most people healthy. However, just as statistical
methods give estimated ranges for 97% of the healthy population,
these same statistical methods also show that most individuals are
likely to have a specific nutrient need that is beyond the curve
-- either unusually high or unusually low.
each nutrient, the same kinds of laboratory tests used in research
to establish RDAs can also be used to determine if an individual
is getting enough to satisfy his or her metabolic needs -- although
getting a full workup of two dozen or more tests can be an expensive
undertaking. Three other options are:
- Ask a nutritional expert about one's health concerns.
- Become familiar with the warning signs of deficiency and of
- Go through a checklist of symptoms of deficiency and of toxicity
of these actions can form the basis for an intelligent dialog with
a health provider as to the best course of action to pursue.
RDAs, AIs and ULs apply only to healthy individuals. People who
are sick have different nutritional needs. Such assessments are
best done in conjunction with one or more experts who are knowledgeable
about both the nutritional and medical aspects of the condition,
including what prescription drugs or other conventional treatments
even though nutritional concerns are vital to both maintaining and
regaining health, an artificial divide has separated them into two
different fields. Most medical doctors have no training or expertise
in nutrition or nutritional therapy, so finding experts who can
coordinate both aspects of this knowledge can be a challenge. For
this reason, SupplementQuality.com has assembled a list of links
to organizations that can help consumers find
one's own personal nutrient needs is a critical and often overlooked
aspect of health maintenance and enhancement. Taking nutrients one
doesn't need is wasteful -- but not getting enough can lead to illness,
with serious consequences both to the individual and society as
RDAs, AIs and ULs provide useful information about aggregate groups
of people, addressing one's specific nutrient needs requires a commitment
to investigation. As a community, we can best address individual
needs not only by developing estimates of what most people need,
but also by having low-cost, easily accessible tests that can pinpoint
potential nutritional deficits before they develop into full blown
RDAs and AIs are "deliberately" kept low in the service of the food
industry or multinational supplement interests is problematic. But
our investigation does reveal that upper intake levels are based
on limited data and unsubstantiated uncertainty factors. To say
that this is bad science seems reasonable; to suggest that such
a situation results more from bureaucratic bias than from objective
investigation seems just as reasonable.
solid quality standards for supplements demands that RDAs and ULs
be based on science, not politics. Better still would be new options
for low-cost testing that can address individual needs for a wide
range of nutritional factors. Widespread availability of such testing
options would offer a substantive basis for optimizing nutritional
programs for both healthy and sick individuals.
the supplement arena, calls for government regulation on one hand
and product "regularization" on the other will increase as academic
researchers, health practitioners and supplement suppliers jockey
for position and standing. Supplement consumers seeking to optimize
their health will benefit from industry-developed quality programs.
However, the level and quality of research needed to reach more
precise knowledge of appropriate nutritional intake levels seems
to be an elusive goal.
supplement industry, academe, health providers and consumers must
recognize the urgent need for better research and widely supported,
third-party industry organizations that are empowered to develop
consensus on standards for supplement purity, content and dosage
levels. Until then, any discussion of recommended minimum or maximum
dosage levels, regardless of their name, will remain controversial.
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to Harmonize Dietary Supplement Regulations." Press release on CRN
website, 20 November 2000. www.crnusa.org/shellnr112000.html.
Fox. "US poor said damaging health with lack of vitamins." Reuters
and MSNBC News, 19 June 2000. www.msnbc.com/news/422857.asp?cp1=1.
Grazian. "Is Vitamin C Harmful?" AltMedicine.com, 13 April 1998.
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Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin,
and Choline. National Academy of Sciences Press, 2000. www.nap.edu.
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K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
Nickel, Silicon, Vanadium, and Zinc. National Academy of Sciences
Press, 2001. www.nap.edu.
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E, Selenium, and Carotenoids. National Academy of Sciences Press,
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Reynolds, PhD, Associate Professor of Human Nutrition and Dietetics,
University of Illinois at Chicago. Personal communication, 14 February
Trumbo, Senior Program Officer, Food & Nutrition Board, Institute
of Medicine, Washington DC. Personal communication, 31 January 2001.
Whitaker, MD; President of the Whitaker Wellness Institute, Newport
Beach CA; author of eight books on nutrition and health; primary
editor of Health & Healing newsletter. Personal communication,
21 January 2001.
Wright, MD; Medical Director of and practitioner with Tahoma Clinic,
Kent WA (www.tahoma-clinic.com);
author of seven books on nutritional and bio-identical hormone therapy,
and of Nutrition & Healing newsletter (monthly print; quarterly
online). Personal communication, 18 January 2001.
RDAs And Safe Upper Levels: Solid Science Versus Bureaucratic Bias:
Recently, the national Institute of Medicine (IoM) has cautioned
that overdosing on vitamin A can cause birth defects and . . .