Vitamin C JAMA Article Critique

In 1970 Linus Pauling, the only person to win 2 Nobel Prizes unshared (no co-contributors), advocated the use of high doses of vitamin C for better health. His book "Vitamin C and the Common Cold" sort of kicked-off America's love-affair with nutritional supplements. Today, vitamin C is the most widely used supplement. In recent years, the media has been publishing anti-vitamin C stories. Three of the four most prominent stories in recent years were: 1) a speculative letter to the editor of Nature about cancer, 2) a preliminary test-tube experiment about cancer that has been retracted, and 3) a paper presented (but never published) at an annual meeting (about vitamin C supposedly clogging arteries - it now appears the vitamin c made the arteries appear thicker in the ultrasound by being healthier rather than by clogging). Extensive work in humans has been done to contradict the negative stories that make headlines. Even the positive journal articles about vitamin C that the media presents as "news" are just repeating studies that were done 50 years ago that demonstrated amazing things the medical community still ignores (in favor of pharmaceuticals) such as very high intravenous doses that could cure things like polio, tuberculosis, and snake bites. I believe the negative reports make headlines because the media knows there is a strong interest in vitamin C and an shocking report that vitamin C causing cancer is going to sell better than a well-done study that says it prevents cancer. However, there has been one well-done study in a respectable journal (JAMA) that I would like to discuss in detail because it has probably had a lasting negative effect on America's health by obscuring the fact that 2 to 10 grams a day of vitamin C will probably add 20 healthy years to the average American (as described in detail in Pauling's books). The JAMA article is an example of how I think good research can still be wacky.

One of America's most famous vitamin proponents, Dr. Andrew Weil, stated in his August 1999 newsletter: "There's now evidence that 200 to 500 mg vit C a day is more than enough to saturate the body's tissues." Dr. Weil cited an April 21st 1999 JAMA article and an Am J Clin Nutr article by the Linus Pauling Institute as the reasons he was lowering his recommendation from 2 to 6 grams per day to 0.2 to 0.5 grams per day. He uses the name of the Linus Pauling Institute twice to bolster his point, failing to point out that Linus Pauling and the institute after which he is named have had dramatically different viewpoints about vitamin C.

Dr. Weil, the Linus Pauling Institute, JAMA, J Clin Nutr, National Institute of Health, and the National Acamdemy of Sciences (the new RDA) all now seem to agree that less than 500 mg a day is needed for optimum health. Here are some reasons many researchers know they are wrong....

Errors in JAMA's 1999 Vitamin C Article

The April 21, 1999 JAMA article on vitamin C by Mark Levine, et al attempted to show by blood and urinary data that vitamin C in doses greater than 100 to 200 mg/day have no useful benefit in humans. The article is important because it strives to guide the new RDA for vitamin C towards 100 to 200 mg/day.

The severity of the inadequacy of the article can be seen by the following observations:

  1. The article recommends an RDA of 100 to 200 mg/day based on arguments that are almost entirely theoretical instead of citing the many real-world studies showing substantial health benefits from levels greater than 1 g/day (including numerous studies on specific diseases done in the 1940's and 1950's - see the 1971 book by Irwin Stone "The Healing Factor - Vitamin C against Disease"). On the internet, an article about high doses can be found at and

  2. The authors do not seemed bothered or amazed that their claims indicate humans need 10 to 100 times less vitamin C than almost every other animal on the planet (adjusted for body-weight). Gorillas get 20 to 40 times as much in their diet and the RDA-equivalent for monkeys is also about 20 to 40 times higher than what the authors are recommending for humans.

  3. The authors' blood and urinary data used to support their suggested maximum recommended daily amount of 100 to 200 mg/d is claimed to be better than data previously available, but article's data and arguments are 20 years old. Linus Pauling in his 1986 book "How to Live Longer and Feel Better" used nearly the exact same blood, urine, and absorption data (pp108-112) to address the exact same misunderstandings to show that 140 mg/d should be considered an absolute minimum instead of a maximum. Pauling detailed why the optimum range of vitamin C for most people is probably between 2.3 and 10 g/d.

  4. By the article's own admission, it recommends an RDA of 100 to 200 mg/day based on faulty data manipulation. The authors chose to measure steady state blood plasma concentrations (which is 8 hours after ingestion) instead of actual real-time concentrations because the calculation for actual concentrations was "too complex". From reading the article's text, one would think 60 umol/L in the blood is as high as can be achieved (which results from ingesting 100 to 200 mg/d). However, by looking at their lower graph in figure 3, the data indicates that if 1,000 mg were taken 4 times a day (approximately the minimum recommendation of several vitamin C experts such as Dr. Cathcart, Dr. Hoffer, Dr. Pauling, Dr. Klenner, and Irwin Stone), it would average out to about 180 umol/L. Obviously a little more calculation (or even some estimating) would have been worth the effort to show a 3-fold increase. Taking 5 hours for blood concentration of vit C to drop to levels that are still 2 times higher than steady state levels is not what I'd call "immediate" excretion as stated in the article. At two hours after the dose, vit C concentration is almost 4 times steady state levels. This data is for 1250 mg. For the support of my statements, see figure 3 and paragraph 2 of page 1418.

  5. The article cites a 1997 article to claim vitamin C in gram doses has no place in the treatment of colds while ignoring a Feb 1999 article by the SAME RESEARCHER that demonstrated 2 g/day reduces the duration of colds in children by 26%. The abstract of that reference is included below. The same effect may be seen in adults if they are given the same amount relative to body weight. Pauling claimed vitamin C would have its greatest effect on the common cold when a gram was taken every hour instead of just once a day.

  6. The authors do not give any physiological explanation for why they believe humans are the only animals that find small doses (1 g/d) of vitamin C "toxic". This size dose has, to my knowledge, never resulted in a human suffering an adverse health effect. The article discusses increased iron absorption and oxalate production. Pauling agreed that heavy doses should be avoided by those who need to avoid foods with oxalate (like spinach) because of a theoretical risk of kidney stones. A Harvard study showed a decrease in kidney stones among those who took over 1.5 g/d. The 1987 book "The Right Dose" by Patricia Hausman states that she was able to find 7 cases of vitamin C being reported as a cause of kidney stones. She states that vitamin C oxalic acid production occurs when over 4,000 mg a day is taken. She also states that those who are susceptible to iron overload should not take vitamin C supplements. She also mentions that tooth enamel decay is a very real danger for those who use chewable vitamin C tablets. The JAMA article's suggested "toxic" level for humans is approximately the bare minimum needed by all other animals. Almost all other animals (especially large mammals) sacrifice 2% to 4% of their daily food energy to make vitamin C from glucose in concentrations 10 to 20 times higher than what the article considers "toxic", showing that not only is it not toxic, but that it's more important than 2% to 4% of the energy acquired from food. Our ancestors probably evolved out one of the genes for making vitamin C probably while under pressure for more food energy and on a high-vitamin C diet (fruits and vegetables) where it wasn't necessary to make as much vitamin C as other animals. However, we are no longer under the threat of starvation and do not have a high vitamin C diet, so supplementation is necessary. Even a glass of orange juice provides only 1/10th as much vitamin C as pauling estimated our ancestors received in their diet (2 to 4 grams a day).
TITLE: Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit.
AUTHOR AFFILIATION: Department of Public Health, University of Helsinki, Finland.
Med Hypotheses 1999 Feb;52(2):171-8
CITATION IDS: PMID: 10340298 UI: 99271657
ABSTRACT: Placebo-controlled trials have shown that vitamin C supplementation decreases the duration and severity of common cold infections. However, the magnitude of the benefit has substantially varied, hampering conclusions about the clinical significance of the vitamin. In this paper, 23 studies with regular vitamin C supplementation (> or = 1 g/day) were analyzed to find out factors that may explain some part of the variation in the results. It was found that on average, vitamin C produces greater benefit for children than for adults. The dose may also affect the magnitude of the benefit, there being on average greater benefit from > or = 2 g/day compared to 1 g/day of the vitamin. In five studies with adults administered 1 g/day of vitamin C, the median decrease in cold duration was only 6%, whereas in two studies with children administered 2 g/day the median decrease was four times higher, 26%. The trials analyzed in this work used regular vitamin C supplementation, but it is conceivable that therapeutic supplementation starting early at the onset of the cold episode could produce comparable benefits. Since few trials have examined the effects of therapeutic supplementation and their results have been variable, further therapeutic trials are required to examine the role of vitamin C in the treatment of colds.

Scott Roberts
December 2, 1999

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