Whole Foods Magazine

July 2000

Vitamin Connection


Antioxidant Recommendations: Part 1 Prudence vs. Absolute Proof

An interview with Drs. Norman Krinsky and Maret Traber


By Richard A. Passwater, Ph.D.


It's unlikely that many of our readers are old enough to remember the introduction to Parry Como's popular request segment oil his television show: "Letters ...We get letters... Lots and lots of letters." Well, I got lots and lots of letters, e-snails and phone calls in mid-April after the official new guidelines oil antioxidant nutrients were released. The goal of this column, therefore, is to explain what the Panel of Dietary Antioxidants and Related Compounds said and didn't say, and what antioxidant supplements are prudent for the public to take to promote optimal health.

The Panel's report actually contains lots of good news, but this may remain buried because few media representatives read the entire, thick report and instead relied on a press release that was very misleading. The Panel's report mentions many positive studies and recommends the large clinical trials that we need to finally prove what decades of research have been showing in animal studies, population studies and small-scale clinical trials. The Panel's report states that there is "reason to expect that antioxidant nutrients should decrease the risk of cardiovascular disease .. and oxidative damage to the eye, thus lessening the risk of cataract." The research suggesting that antioxidant nutrients may protect against heart disease by preventing the cholesterol carrier called low-density lipoprotein from being oxidized also is discussed.

It may be taken as additional good news that the Recommended Dietary Allowances (RDAs) for vitamins C and I: were raised, and that the newly established tipper limits for dosages are above those normally considered "megavitamin" levels. When I published Supernutrition: Megavitamin Revolution in 1975, megavitamins were a new concept, and the public was told that these levels were dangerous. Now we know that even much higher dosages are safe.

I have called on two of the Antioxidant Panel members to elaborate on what the report truly says, and then look at the new RDAs. Dr. Norman Krinskv of Tufts University, the Panel's chairman and Dr. Maret Traber of the Linus Pauling Institute and Oregon Slate University will discuss the "real" messages of the report to clarify what the media reported. In Part 2 of this series, Dr. Jeffrey Blumberg of Tufts University will discuss additional facts about our antioxidant nutrient needs. In Part 3, Drs. Denham Harman, of the University of Nebraska School of Medicine and father of the free-radial theory of aging, Balz Frei, director of the Linus Pauling Institute at Oregon State University, and Dr. Blumberg, will chat with us about what various studies tell us about the health benefits of antioxidant nutrients in levels above the RDA, the safety of antioxidant nutrients, and the scare reports recently published about vitamin C and other antioxidants.

This is not an adversarial debate. Antioxidant researchers interact at various conferences throughout the year, and we are familiar with each other's research, experience and viewpoints. We have a great deal of respect for each outer. We actually agree on most issues, but take exceptions to some. We look at the same facts, the same total body of knowledge, but due to our differences in other research experiences, personal experience and personalities, we often have differences in the interpretation of the data.

As an example, as a result of my writings, I have received input from thousands of people who attest to the personal beneficial impact antioxidants have had on their lives. While other scientists often feel that such anecdotal accounts are not scientific, I believe the totally consistent character of these thousands of reports qualifies as a valid study, even though it doesn't meet the rigid requirements of a double-blind, placebo-controlled, crossover clinical trial. If other scientists received some of these thousands of letters from all over the world-with their "God Bless you" and/or "thank you for saving or improving my life" commentary-they would look at the existing data with what I feel would be a more informed perspective.

This column examines both the agreements and disagreements of antioxidant researchers in much the same way we cordially express our sentiments to each other at scientific sessions. At the same time, the column attempts to repair the damage done by what some of us feel was an inappropriately worded press release.

It seems that the official press release from the National Academies of Science may have influenced a large component of the media to miss the point or misinterpret what the expert I panel said, didn't say and wanted to say. This, coupled with the fact that many people heard only part of what was being said because their ears didn't pert up until midway through the news stories, encouraged many of our readers to contact me about "my opinion" about the antioxidant nutrient reports.

The official press release issued by the National Academies was headlined "Antioxidants' Role in Chronic Disease Prevention ,Still Uncertain: Hugh Doses Considered Risky" Apparently, many in the media tool this headline as the equivalent of AAntioxidants Don=t Work@ and /or@ Antioxidants in Pill Form Are Harmful.@ It is not surprising then that The Washington Post ran a lead front-page article entitled APanel Calls Antioxidant Megadoses Ineffective.@ Well, that=s not what the panel said. Sometimes reporters don=t seem to understand the difference between scientifically cautious phrases such as Ainadequate evidence to be proven effective@ and A proven to be ineffective.@

Fortunately, some of the media got it right. CBS called in former National Institutes of Health Director, and now the president of the American Red Cross, Dr. Bernadine Healy to properly explain the Panel=s report. On an early Saturday morning, April 15, Dr. Healy was interviewed by co-host Thalia Assuras, and this is part of the exchange:


Assuras: And if you are one of the millions of Americans who take massive doses of antioxidants, such as vitamin C and E, well, a government panel said this week you might be wasting your money even harming yourself.

Healy: Well, the real headline here is that the panel of the U.S. government that sets those RDAs, the recommended daily food allowances, came out and said, "Increase the number of antioxidants in your diet, specifically increase vitamin C from roughly 60 mg up to 75 mg for women, 90 mg for men. And, if you are a smoker, add on 35 mg. They also recommended an increase in vitamin E, another antioxidant, to 15 mg. And that is almost a doubling in the case of women.

Assuras: But there is it point when there's too much. How much is too much?

Healy: Massive amounts of vitamins are where you may be getting into it toxic range. But that's not the same thing its the so-called megavitamins, which are in between and are the things that many scientists are hopeful might, in fact, decrease your chance of having some of these diseases

Assuras: If you get to the massive level or the extreme level, however, there are serious health problems? Is that correct?

Healy: Well, for vitamin C, it goes right through your body into your urine, so there--there really are not serious side effects, although it can cause some tummy problems and diarrhea. With regard to vitamin E, it's lipid soluble, it hangs around in your body awhile and it can affect blood clotting, your platelets, particularly as you increase on to the dosages.

Assuras: Where did the belief that large doses of some of these antioxidants can actually help in preventing diseases come from?

Healy: Well, there's been a literature developing over 20 years from public health studies, from looking at people who take these dietary supplements, the vitamins, and also from just testing blood levels of these vitamins that consistently tends to point to the fact that certain major problems like heart disease and heart attacks-and, in some cases, some cancers-and cataracts and aging, may be linked to how much of these antioxidants you have in your diet. The more you have, it appears that you have less of these diseases or your risk is lowered. Maybe even Alzheimer's disease has had that link .... You're looking at maybe 200 or 300 mg of vitamin E, maybe 500 to 1,000 mg of vitamin C, much below that toxic level that the report is suggesting. The important thing, is what this report said is, ".We're not prepared yet, there's not enough rock solid evidence to, to say yes, all Americans, take those megavitamins." So they took a more conservative stance. They increased the recommended dosages, but they didn't move into the mega level yet.

Even though the interviewer appeared to start off with a misunderstanding of the report from the National Academies, both she and CBS News should be given credit for letting Dr. Healy have her full say.

What Are RDAs?

Among other things, Dr. Healy mentioned that the new report increased the recommended dosages, the RDAs. The RDAs are now set by the Food and Nutrition Board (FNB). The FNB was established in 1940 under the division of Biology and Agriculture of the National Research Council (NRC). The FNB is now a unit of the Institute of Medicine (IOM) which was chartered in 1970 as part of what was then known as the National Academy (now Academies) of Sciences (NAS) According to information provided by the NAS, it is a private, nonprofit corporation created by an Act of Congress, with a charter signed in 1863 by President Abraham Lincoln. The IOM acts as an adviser to the federal government on issues of medical care, research, and education. The IOM secures the services of members of appropriate professions to examine policy matters pertaining to the public's health, and occasionally undertakes studies on its own initiative.

The FNB is a multidisciplinary group of biomedical scientists with expertise in various aspects of nutrition, food science, biochemistry, medicine, public health, epidemiology, food toxicology, and food safety. The FNB receives funding from federal agencies such as the FDA, USDA, NIH and CDC to evaluate issues concerning food and nutrition.

In the past, the RDAs published by the FNB have served as the benchmark of nutrition adequacy in the United States. The traditional role of the RDAs is described by its definition adopted snore than 20 years ago: "The levels of intake of essential nutrients, that, on the basis of scientific knowledge, are judged by the FNB to be adequate to meet the known needs of practically all healthy persons."

The problem with this definition is the word "needs." Needs for what? Growth? Average health, which, in today's world, translates into an individual having a major operation every decade and a high risk of heart disease and cancer? Certainly, the RDAs do not address optimal health and the prevention of chronic diseases. However, the FNB claims that they wish to now address the risk of chronic disease.

The FNB now states, "Scientific knowledge regarding the roles of nutrients has expanded dramatically since the inception of the RDAs. Contemporary studies address topics ranging from the prevention of classical nutritional deficiency diseases, such its rickets, to the reduction of risk of chronic diseases such as osteoporosis, cancer and cardiovascular disease. This expansion has extended the basis for the developments of Dietary Reference Intakes (DRIs)."

According to the FNB, DRIs is a generic term used to refer to at least three types of reference values: Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), and Tolerable Upper Limit Intake Level (UL). EAR is the intake value that is estimated to meet the requirement defined by a specified indicator of adequacy in 50/ of an age and gender-specific group. At this level of intake, the remaining 50%, of the specified group would not have its needs met.

The RDA is the dietary intake level that is sufficient to meet the nutrient requirements of nearly all individuals in the group. The Eighth Edition (1974) states, "RDA should not be confused with requirements. Differences in the nutrient requirements of individuals that derive from differences in their genetic makeup are ordinarily unknown." Thus, the principles of Dr. Roger William's "biochemical individuality" are well taken.

The RDAs should not be confused with the United States Recommended Daily Allowances (USRDA), a set of values derived front RDA by the Food and Drug Administration (FDA). These formerly were used as standards for nutritional labeling. Now, however, Daily Values (DVs) are used for food products. These DVs should not be confused with RDAs either. As an example, if a label states that a serving contains 100% of the daily value (DV) for vitamin C, that is not 100% of the RDA for vitamin C. The DV for vitamin C set by the FDA is 60 mg/day. This DV is 80% of the new RDA of 75 mg/day for women and 67% of the new RDA of 90 mg/day for men.

Here's another example: if the label claims 100%, of the daily value (DV) for vitamin E, that too would not be 100% of the RDA. The DV set by the FDA for vitamin E is 30 IU/day of dl-alpha tocopheryl acetate, which equates to 13.5 mg/day of alpha-tocopherol. The DV is 90% of the new RDA of 15 mg/day of alpha-tocopherol for adults.

The UL is the maximum level of daily nutrient intake that is unlikely to pose risks of adverse health effects to almost all of the individuals in the group for whom it is designed.

RDAs Over The Years

When I began my research with antioxidant nutrients, neither vitamin E nor selenium was proved to be of use in human. Not only were there no RDAs, there were no proved usages of either in the human body. I vividly remember in 1957 when the FDA issued press releases and articles essentially saving that vitamin E supplements were a waste of money, as vitamin E had no role in humans. As you can see in Table 1, the RDA for vitamin E was established in 1968. In spite of what the FDA articles said, the RDA committee recognized that vitamin E was essential for many animals and they commented that there might be a need for vitamin E in humans, although it was not shown to be essential for humans in any studies at that time. However, many of us felt that it was prudent to take vitamin E supplements. The RDA for selenium did not exist until an "adequate and safe range" was proposed in 1980.

Let's look at the recommendation for the antioxidant nutrients vitamin C, vitamin E and selenium as they have evolved over the years. The first recommended allowances, developed as a guide for advising on nutritional problems in connection with national defense, were announced in May 1943.(1) They included calories and nine nutrients. These RDAs were revised in 1945, 1948, 1953, 1958, 1963, 1968, 1974, 1980 and 1989.(2-10) In 1999, a new system was introduced, calling for several reports to be issued over a period of lime fur different groups of nutrients. (ll) There have been three reports issued so far under the new system: Calcium etc. B- Vitamins, and the Antioxidants. (12,13) Table 1 lists several of the RDAs for, vitamin C, vitamin E and selenium in several editions of [he RDA.


What Really Was Said

OK, this rather long preamble now completed, let=s look al what the, Antioxidant Panel actually said and what their message really is. And to help us in this analysis, we are invoking the assistance of Drs. Norman I. Krinsky and Maret Traber.

Dr. Krinsky is the chairman of the Panel of Dietary Antioxidants and Related Compounds. He is a professor of biochemistry at Tufts University School of Medicine and scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. He has published more than 40 articles related to antioxidants, with emphasis on carotenoids.

Dr. Traber is an associate professor in the Department of Nutrition and Food Management at Oregon State University and also at the Linus Pauling, Institute. Readers may recall our three-part vitamin E interview with Dr. Traber, which appeared in Whole Foods, November 1997 through January 1998.

Passwater: Dr. Krinsky, let me play the rule of the devil's advocate here so that 1 can draw out for our readers exactly what the Panel reported. Just what were the findings of the Panel regarding the efficacy o1 dietary antioxidants?

Krinsky: In essence, the report summarizes the available research and establishment the Dietary Reference Intakes (DRIs) for antioxidant nutrients related compounds. We concluded that although numerous studies have suggested that there may be a connection between the intake of antioxidants and the prevention of chronic diseases such as cancer, heart disease, and eye diseases such as cataract and age- related macular degeneration, were not convinced that sufficient data were available at this time The Panel recommended that more controlled studies be carried out to evaluate whether the reported associations between antioxidants and chronic disease are sufficiently sound to make a different recommendations in the future.

Vitamin C (mg) Vitamin E (IU) Selenium (mcg)

Edition Year M F M F M F

First 1943 75 70 * * * *

Second 1945 75 70 * * * *

Third 1948 75 70 * * * *

Fourth 1953 75 70 * * * *

Fifth 1958 75 70 * * * *

Sixth 1963 70 70 ** ** * *

Seventh 1968 60 55 30 25 *** ***

Eighth 1974 45 45 15 12 *** ***

Ninth 1980 60 60 10 8 50-200 50-200

Tenth 1989 60 60 10 8 70 55

** 2000 90 75 15+ 15+ 55 55

+ Present recommendations for vitamin E are measured in mg of alpha-tocopherul

++ Dietary Reference Intakes for Vitamin C. Vitamin E, Selenium, and Carotenoids (2000)

* No mention of being essential for humans

* * Considered essential for humans, but no RDA

*** May have a function in humans




Passwater: You mentioned that there may be a connection between the intake of antioxidant nutrients and the prevention of disease, but the Panel doesn't find sufficient data. What do you accept?

Krinsky: We do know that dietary antioxidants can in some cases prevent or counteract cell damage that sterns from exposure to oxidants, which are agents that affect a cell's molecular composition. But much more research is needed to determine whether dietary antioxidants actually can stave off chronic disease.

Passwater: How much evidence is required before the Panel feels that there is adequate data? Dr. Traber, did the Panel consider any of the data "good" evidence that antioxidants reduce chronic diseases?

Traber: It would help if people would read the actual report rather than relying on news accounts of the report. We were charged with defining the minimum amount of a nutrient that has beneficial health effects. Largely, the effects of antioxidant nutrients and their relationship to chronic diseases are "promising, but not yet proven." The difficulty is proving that antioxidants have a role in prevention or amelioration of chronic disease. Unfortunately, there is little information available from studies of requirements in normal humans.

Passwater: Did the Panel find data that they could consider good evidence that antioxidant supplements may help people live better for a longer period of time?

Traber: It is not that there is no good evidence, there is no evidence that proves antioxidant supplements will help people live better longer.

Passwater: What type of evidence is required before an RDA Panel can state that antioxidant supplements are beneficial?

Traber: "Are" versus "may be" is the key here. Antioxidants may be beneficial. This was not considered sufficient evidence to make policy statements that every person consume larger amounts.

Passwater: What did the Panel say about the safety of vitamin C and vitamin E Supplements?

Traber: The report said for vitamin E, 15 mg of alpha tocopherol is required, and that more than 1,000 mg may have adverse effects. The public may choose to consume a diet that is rich in nuts, seeds. whole grains and leafy green Vegetable to get the 15 mg, or they may decide that their diet is relatively poor in these foods, and they do not want to increase their consumption of plant oils (e.g. sunflower. canola, olive oils) or they may have read the evidence that some benefit has been observed in some trials and decide a supplement would benefit their personal situation. The Panel simply said that people should not take more than 1,000 mg of alpha tocopherol daily; it did not say they should not take supplements.

With respect to vitamin C, if people followed the current recommendations about eating five to seven servings of fruits and vegetables a day, they easily would exceed the recommendation of 90 mg per day for men. Nonetheless, the Panel recommended that if one chooses-based on a personal evaluation-that supplements of vitamin C are useful, then do not exceed 2,000 mg daily. Again, we did not say that people should not take supplements.

It was disappointing that the media focused on the "new" upper limits (ULs) for vitamin C, vitamin E and selenium, rather than the "new" requirements.

Hopefully, it will be noticed that we now recommend the only form of vitamin E that meets the human nutritional requirement. This is alpha tocopherol. As we have previously discussed in this column, this is based on the structural requirements of the alpha tocopherol transfer protein. Thus, gamma tocopherol does not meet the requirement (alpha tocopherol equivalents are not recommended). Moreover, only half of the stereoisomers in synthetic vitamin E (dl-alpha tocopheryl acetate) meet the requirement. This means that the consumer would have to eat twice its much synthetic as natural vitamin E to meet the requirement.

Passwater: Well, thanks to your three part chat with us in 1997-8, hopefully, our readers know this. The Panel raised the RDA for vitamin E a little, but aren't most Americans falling below this intake level?

Traber: The amount of vitamin E consumed by American adults is about 8 mg a day. It isn't clear whether chronic disease such as heart disease and cancer are a hallmark of these long-term, sub-optimal vitamin E intakes. But, higher intakes of vitamin E may be beneficial if chronic diseases such as heart disease, stroke, cancer, diabetes, and Alzheimer's disease result in part from sub-optimal protection by antioxidants.

The amount of vitamin E that had beneficial effects in epidemiological studies was more than 100 mg per day an amount not achievable by normal dietary means, but easy to provide by inexpensive supplements.

Passwater: Thank you Dr. Krinsky and Dr. Traber for explaining some of the important facts about the report. In Part 2, we will chat with Tufts University's Dr. Jeffrey Blumberg to learn more about antioxidant nutrients and the supporting research that suggests that antioxidant supplements may help protect us from chronic diseases. WF



I. National Research Council, Recommended Dietary Allowances. Reprint and Circular Series No. 122, Washington, 1).C. (1943)

2. National Research Council, Recommended Dietary Allowances, Revised 1945, Reprint and Circular Series No. 122, Washington, D.C. (1945)

3. National Research Council, Recommended Dietary Allowances, Revised 1948, Reprint and Circular Series No. 129, Washington, D.C. (1948)

I. National Academy of Sciences-National Research Council, Recommended Dietary Allowances, Revised 1953, Publ. No. 302, Washington, D.C. (1953)

5. National Academy of Science-National Research Council, Recommended Dietary Allowances, Revised 1958, Publ. No. 589, Washington, D.C. (1958)

6. National Academy of Sciences-National Research Council, Recommended Dietary Allowances, Revised 1963, Publ. No. 1116, Washington, D.C. (1964)

7. Recommended Dietary Allowances, Seventh Revised Edition, 1968; Publ. No. 1691. National Academy of Sciences, Washington D.C. (1968)

8. Recommended Dietary Allowances. Eighth Revised Edition, 197$1; National Academy of Sciences, Washington, D.C. (1974) 9. Recommended Dietary Allowances. Ninth Revised Edition, 1980; National Academy of Sciences, Washington, 1).C. (1()80) 10. Recommended Dietary Allowances, 101h Edition, National Academy Press, Washington, D.C. (1989)

I In. Dietary Reference Intakes for Vitamin E, Vitamin C, Selenium and Carotenoids (2000). National Academy Press, Washington. D.C.


1'2. Dietary Reference Intakes for Calcium. Phosphorus, Magnesium, Vitamin I), ;111(1 fluoride. National Academy Press, Washington, D.C. (1997)

13 Dietary Reference Intakes for Thiamin. Riboflavin, Niacin, Vitamin 136, Folate, Vitamin 1112, Pantothenic Acid, Biotin, and Choline. National Academy Press, Washington, 1).C. (19<.)8)

2000 Whole Foods Magazine and Richard A. Passwater, Ph.D.

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