RDAs And Safe Upper Levels: Solid Science Versus Bureaucratic Bias  (continued)

Safe 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 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.

When 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!

Adverse events or useful treatment?

Take 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."

Nutritional 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.

Vitamin 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.

In 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."

So 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?

Safe upper levels: Erring on the side of caution

A 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.

There 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.

Rather 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 uncertainty factors and UL calculation.)

While providing a safety cushion in the form of an uncertainty factor may be laudable, what is "uncertainty" really all about?

Fudge factors not so sweet

Phosphorus 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.

However, 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.

While 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.

"Excessive safety" and nutrient availability

On 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.

The 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.

(Vegetarians 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.)

However, 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.

There 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.

Reduced 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.

Potential impact of international "harmonization"

Ongoing efforts to "harmonize" the US and European regulatory environments could have an equally serious impact on the availability and accessibility of supplements.

Both 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:

"Define 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."

The 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.

RDAs and safe upper levels: Is there a better alternative?

Because 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.

Just 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.

Dr. 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 health problems."

When 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."

As for safe upper levels, Dr. Wright offers this observation:

"Across-the-board 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."

Functional measures of nutritional adequacy

A 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:

"It's 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."

Dr. 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."

Also 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."

"Little gray cells" and what works best

As 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 "whodunit".

Here, 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 to take.

So 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.

For 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:

Any of these actions can form the basis for an intelligent dialog with a health provider as to the best course of action to pursue.

Also, 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 are valuable.

Unfortunately, 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 supplement-savvy doctors.

Conclusion

Understanding 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 a whole.

While 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 illness.

Whether 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.

Developing 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.

In 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.

The 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.

Sources

Council for Responsible Nutrition. "U.S. and European Leaders Agree on Principles to Harmonize Dietary Supplement Regulations." Press release on CRN website, 20 November 2000. www.crnusa.org/shellnr112000.html.

Maggie 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.

Frank Grazian. "Is Vitamin C Harmful?" AltMedicine.com, 13 April 1998. www.altmedicine.com.

Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. National Academy of Sciences Press, 1997. www.nap.edu.

Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy of Sciences Press, 2000. www.nap.edu.

Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy of Sciences Press, 2001. www.nap.edu.

Institute of Medicine. Dietary Reference Intakes for vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy of Sciences Press, 2000. www.nap.edu.

Richard A. Passwater. "Vitamins, Immune Response and Safety -- an Interview With Dr. Adrianne Bendich." Whole Foods Magazine and HealthWorld Online, date estimated as 1995 or 1997 by HealthWorld Online. www.healthy.net/asp/templates/Interview.asp?PageType=Interview&Id=159.

Robert Reynolds, PhD, Associate Professor of Human Nutrition and Dietetics, University of Illinois at Chicago. Personal communication, 14 February 2001.

Paula Trumbo, Senior Program Officer, Food & Nutrition Board, Institute of Medicine, Washington DC. Personal communication, 31 January 2001.

Julian 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.

Jonathan 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 . . .