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"RDAs and safe upper levels are more political than scientific."

An interview with Professor Robert Reynolds of the University of Illinois at Chicago.
14 February 2001


The national Institute of Medicine (IoM) is charged with the task of establishing recommended intake levels of vitamins and minerals. The IoM is part of the National Academy of Sciences, a non-governmental organization that is chartered to advise the government on scientific matters.

The IoM recently published new guidelines for vitamins A and K and seven important minerals. We read some of the fine print in this and three other IoM reports (published in 1997 and 2000), and discovered what appeared to be more than a few gaps and questionable conclusions. We contacted several universities looking for expert opinion that was independent of both the IoM and supplement sales or prescribing organizations, and found Professor Reynolds.

Reynolds has spent over 30 years conducting research on the normal and abnormal metabolism of vitamin B6 as it relates to disease and health. His work has focused on a wide range of subjects -- including normal healthy adults, pregnant and lactating women, infants, and seniors -- and a wide range of diseases and disease conditions, including rickets, HIV, sickle cell anemia, and drug-resistant tuberculosis. Professor Reynolds also teaches courses on vitamins and minerals at the University of Illinois at Chicago.

Via telephone, we discussed our concerns about RDAs and safe upper levels with him.

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?

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.

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.

SQ: Such as having little or no data about men's needs for calcium or children's needs for vitamin C.

A: Exactly.

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 .

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).

A: Yes -- but the key word there is estimated.

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."

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.

SQ: How is it possible that the IoM makes decisions like this, and then presents them to the public as solid science?

A: The RDAs and AIs are more political than scientific.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A: A lot of that increase in the RDA for vitamin C is a result of political pressure.

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.

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?

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.

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.

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.

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.

A: The upper level is calculated using an uncertainty factor. These uncertainty factors are totally arbitrary and politicall.

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).

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.

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.

SQ: What about the overall usefulness of RDAs? Do they appy to everyone?

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."

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."

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.

A: It's worse than that. Do you smoke?

SQ: No.

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.

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.

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.

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 . . . ?end-of-story

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.



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