Vitamin C: Do High Doses Prevent Colds?

Charles W. Marshall, Ph.D. (Edited by Stephen Barrett, M.D)

Few things have stirred the imagination and hopes of the public in matters of nutrition or vexed nutrition scientists as much as Linus Pauling's 1970 book, Vitamin C and the Common Cold. [1] The book's main claim was that taking 1 gram (1,000 mg) of vitamin C daily would reduce the incidence of colds by 45% for most people, but that some persons might need much larger amounts. It recommended that if symptoms of a cold do start, you should take 500 or 1,000 mg every hour for several hours – or 4 to 10 grams daily if symptoms don't disappear with smaller amounts. Without question, publication of this book, combined with Pauling's reputation as a Nobel Prize-winning scientist, has made vitamin C a best seller. When his theory was announced, millions of Americans rushed to try it for themselves. The second edition of the book, issued in 1976 as Vitamin C, the Common Cold and the Flu, suggested even higher dosages [2].

Vitamin C and the Common Cold also suggested that most people need a daily vitamin C intake of 2,300 mg or more for “optimum” health and to meet stresses, including infections. In a subsequent book, How to Live Longer and Feel Better, Pauling stated that individual biochemical variability is so great that optimum intake may may be as great as from 250 mg to 20 grams or more per day [3].

Many concerned persons have wondered whether Pauling's advice was prudent, and millions have experimented upon themselves to see whether they could tell. Pauling himself reportedly took 12,000 mg daily and raised it to 40,000 mg when symptoms of a cold appeared! [4] Pauling apparently adapted to such dosage, but most people would suffer chronic diarrhea and the risk of kidney stones. Also, the vast majority of reputable medical and nutritional scientists strongly disagree with him. Before looking at the experimental evidence, let's discuss how scientists form their opinions. How Scientific Facts Are Determined

The “scientific community” consists of thousands of scientists throughout the world, most of whom operate under a strict set of rules known as the scientific method. Simply stated, this is a system of logical steps designed to separate cause-and-effect from coincidence. This method is used to answer such questions as: “If you do a particular thing, will something else take place?” and “If two things follow one another, are they related?”

A scientific “fact” is determined by analyzing the results of all the experiments that bear on that particular fact. In the case of vitamin C, there are two key questions. First, does vitamin C prevent colds? And second, does it reduce their severity? Before discussing experiments on these questions, however, we should note that not all experiments are created equal. To be valid, an experiment must be well designed, and Its data must be honestly collected and Interpreted with good techniques of statistical analysis. One hallmark of a good experiment is that others can repeat it and get the same results.

Experimental studies of the possible value of vitamin C in the prevention of infections have been conducted by medical investigators ever since preparations of the pure crystalline vitamin became commercially available during the 1930s. By 1982, about thirty of these were reported and the majority of medical scientists had concluded that supplementation with vitamin C does not prevent colds and, at best, may slightly reduce the symptoms of a cold. Two subsequent reports have not altered these findings.

Linus Pauling remained steadfast in his belief that the scientific community was wrong – basing his ideas on the same experiments but interpreting their results differently. Moreover, he suggested the following way to determine one's correct vitamin C dosage: “If you are taking 1 gram [1,000 mg] per day, and find that you have developed two or three colds during the winter season, it would be wise to try taking a larger daily quantity.” Presumably, if you have fewer colds than expected, you should believe that vitamin C has been responsible for the decrease.

Unfortunately, in the real world, scientific facts cannot be determined that simply. Consider the following questions:

   * Is it possible that you actually had a different number of colds than you recall? This would be faulty data collection.
   * Is it possible that you would have had only one cold this year anyway? If so, what happened to you would be a mere coincidence.
   * Is it possible that you had a very mild cold but wish so strongly for a favorable result that you didn't count it? If so, this would be an effect of bias. 

Scientific experiments must be designed to overcome these possible sources of error. The problem of faulty memory can be overcome by keeping close track of the individuals involved in an experiment. The problem of coincidence can be overcome by using large numbers of people and following them for significant lengths of time. The problem of bias, however, is far more complicated. Use of the double-blind method is critical, but as you will see, experiments with vitamin C have encountered some very curious results when subjects were able to figure out whether they were getting the vitamin or the placebo during experiments intended to be double-blind.

So far, at least 30 experiments have tested the ability of vitamin C to protect against colds in large groups of people. Four biomedical scientists who have analyzed the results of these trials have found Pauling's claims unsupported, except for slight reduction in severity, in most of those trials that were scientifically properly designed and executed [5-8]. Now let's examine the evidence. Well-Designed Experiments

One way to test whether high-dosage vitamin C prevents colds is to inoculate the throats of volunteers with cold viruses. Two studies of this type found that everyone got colds whether they took vitamin C or not. Walker and co-workers in 1967 and Schwartz, Hornick and associates in 1972-73 gave half of their volunteers a placebo and the rest 3,000 mg of vitamin C daily for several days before inserting live cold viruses directly into their noses; and then continued 3,000 mg of vitamin C (or placebo) for seven more days. All of the volunteers got colds, which were of equal severity [9-11].

Another way to test vitamin C is to see what happens to matched groups over a period of time. Two teams of investigators have done this more than once, one team led by Dr. John L. Coulehan and the other by Dr. Terence Anderson. Dr. Coulehan's first study was done on 641 Navajo Indian children, half of whom received a placebo while the rest received 1,000 mg of vitamin C daily. A complicated system of judging the severity of head, throat and chest symptoms was used. The Coulehan team reported in 1974 that the vitamin C group had less severe colds, but other scientists who reviewed the study criticized the method of judging the severity of symptoms [12].

So in 1976 the Coulehan team repeated their study with 868 Navajo children but used a better system of scoring severity. The children receiving vitamin C averaged 0.38 colds per person while the placebo group averaged 0.37. The average duration of the colds was 5.5 days in the vitamin group and 5.8 in the placebo group. Thus, in this test, vitamin C neither prevented colds nor shortened their duration [13]. In 1979, Dr. Coulehan published his analysis of vitamin C versus the common cold and concluded that extra vitamin C is not worth taking [14].

In 1972, Dr. Terence Anderson and colleagues at the University of Toronto published the results of a 3-month double-blind study of 818 volunteers aged 10 to 65. Half received 1,000 mg of vitamin C daily before colds and 4,000 mg per day during the first 3 days of a cold, while the other half received “equivalent” placebos [15]. This study was designed to test Pauling's claims that ingestion of 1,000 mg of vitamin C daily would reduce the frequency of colds by 45% and the total days of illness by 60%. These claims were certainly not supported by the study's outcome. In the vitamin group, 74% had one or more colds during the study period while 82% of the placebo group had one or more colds. The difference, which amounted to “one-tenth of a cold per person,” was judged by Dr. Anderson to be “of no practical importance.” The severity, as measured by days confined indoors, averaged 1.36 days for the vitamin group and 1.87 days for the placebo group – a 30% difference that Anderson decided to explore further. At the end of this trial, before the double-blind code was opened, all volunteers were asked whether they had experienced any unusual feelings of well-being [euphoria] during the trial. Nineteen percent of both groups said yes – an interesting example of the placebo effect

In 1974, the Anderson team , reported on a larger trial to see what results would be obtained with different amounts of vitamin C [16,17]. Some 3,500 volunteers were divided into eight groups, six of which received various daily dosages of vitamin C while the others received placebos for 3 months. No difference in the incidence of colds was found among the groups taking no vitamin C, 250 mg, 1,000 mg or 2,000 mg daily. A possible slight reduction in severity of symptoms was found in the vitamin C groups, but volunteers taking dosages of 4,000 or 8,000 per day when a cold began did no better than those taking only 250 mg per day.

The third Anderson trial, reported in 1975, covered 16 weeks and used 488 volunteers (ages 14­67), with one-third receiving a pill of vitamin C as its sodium and calcium salts, and one-third given vitamin C in slow-release capsules, and one-third getting a placebo [18]. The vitamin C dosage was 500 mg once a week (equivalent to about 70 mg daily) before colds, but 1,500 mg the first day of a cold followed by 1,000 mg on the second and third days. No reduction in the incidence of colds was observed, but those taking vitamin C averaged less time at home (1.62 vs. 1.12 days indoors). Do you think that a half-day's less confinement is of practical significance?

Taken together, the Anderson studies suggest that extra vitamin C nay slightly reduce the severity of colds, but that it is not necessary to take the high dosages suggested by Pauling to achieve this result. Nor is there anything to be gained by taking vitamin supplements year-round in the hope of preventing colds.

In 1975, Carson and co-workers reported treating company employees with 1,000 mg of vitamin C or a placebo daily during colds. The number of colds per person, the duration of colds and their severity were the same in both vitamin and placebo groups [19].

In 1975, Karlowski and associates at the National Institutes of Health reported treating volunteers as follows: 25% received placebos; 25% took 3,000 mg of vitamin C daily before colds but placebos during colds; 25% were given placebos daily before colds and 3,000 mg of vitamin C daily during colds; and 25% got 3,000 mg daily before colds and 6,000 mg daily during colds. The experiment was supposed to be double-blind, but the doctors had failed to make the placebo taste the same as the vitamin C pills as is done in most trials. As a result, half of the volunteers correctly guessed which pill they were getting and therefore became unblinded. When the results were tabulated with all volunteers lumped together, the average number of colds per person was 1.27 colds for the vitamin group and 1.41 for the placebo group. But among those who remained blinded, no differences in the incidence or severity were found [20]. This fascinating result shows how many people who think they are taking a positive step (such as taking a vitamin) may report a favorable result even when none really exists!

In 1977, Miller and colleagues 22 treated 44 pairs of identical twins for 5 months as follows. One twin in each pair received a vitamin C capsule while the other got a placebo. The daily vitamin C dosages before and during colds ranged from 500 for younger children to 1,500 mg for older ones. The investigators noted “no significant overall benefit on cold symptoms” as reported by the children's mothers, but the responses varied among the subgroups when the children were divided according to sex and age [21]. After the data were analyzed, four mothers admitted tasting the capsules in an attempt to figure out which twin was getting the vitamin C! Thus it is possible that the ratings of these mothers and possibly others were influenced by guessing which twin was getting the vitamin C.

Two studies using identical twins have been reported. In 1977, Tyrell and co-workers reported treating 743 men and 758 women for 5 months as follows. Half received placebo pills daily. The others took vitamin C but only during colds at these dosages: 4,000 mg on the first and second days of a cold and 200 mg on the third day. There was no benefit from taking vitamin C. The incidence and duration of colds were the same for both men and women in the vitamin and placebo groups [22]. Men in both groups missed an average of half a day's work while women missed about a day [23]. The other study, reported in 1981, used 95 pairs of identical twins. One of each pair took 1,000 mg of vitamin C for 100 days while the other received a placebo The vitamin C group had slightly more colds but a shorter duration of colds (5 days instead of 6). [23]

An 8-week trial with 764 Marine recruits carried out by Pitt and Costrini was reported in 1979. Half of the recruits received 2,000 mg of vitamin C daily, while the others took placebo pills on the same schedule. No benefit from vitamin C was found. Ninety percent of both groups got colds, and no difference in severity or duration of colds was found [24].

In a 1984 study, Dr. X. H. Briggs 26 divided 528 volunteers and gave half 1,000 mg vitamin C daily and the other half a daily placebos for three months. In the vitamin C group 47% got colds, and 46% of the placebo group. Severity of symptoms lasted on average 3.1 days for the vitamin C group and 3.3 days for those getting placebos. Briggs concluded: No prevention and no benefit [25].

In 1990, Dr. Elliot Dick and coworkers summarized the methods and results of their three double-blind controlled trials to test methods of transmission of viruses, by contaminated fingers or inhaling viruses in the air, and to test the protective effect of vitamin C. They used 24 volunteers, 8 donors and 16 recipients. The recipients were nonsmoking men testing negative for antibodies to the RV16 type cold virus. Half were pretreated for 3 1/2 weeks with 2,000 mg of vitamin C daily (4 x 500 mg), and the other were eight given 4 placebos daily. The eight donors were infected with RV16 cold virus by direct inoculation into the nose and then were housed with the recipients 24 hours a day for a 7-day interaction period. All donors developed colds first and then all 16 of the recipients. The vitamin C or placebo pills were continued during the week of interaction and for the following two weeks. During the 7-day interaction period the men were supervised and slept, ate and played cards in the same room. Results: All got colds [26].

In 2001, an Australian team published the results of a double-blind, randomised clinical trial with four intervention arms: vitamin C at daily doses of 0.03g (“placebo”), 1 g, 3g, or 3g with additives (“Bio-C”) taken at onset of a cold and for the following two days. The study included 400 healthy volunteers who were followed over an 18-month period. The participants were instructed to take the pills when they had experienced early symptoms of a cold for four hours, and to record daily their symptoms, severity, doctor visits, and use of other medications. Among the 149 participants who returned records for 184 colds, no significant differences were found from one group to another [27]. Do Added Bioflavonoids Help?

In 1979, Dr. I. M. Baird and co-workers reported ona 10-week experiment with 350 volunteers (ages 17 to 25) who were divided into 3 groups. One-third of them, as the placebo group, received a daily “supplement” of a synthetic orange drink containing no vitamin C. A second group got a synthetic orange drink containing 80 mg of synthetic vitamin C. The third group was given enough pure orange juice daily to provide 80 mg of natural vitamin C plus bioflavonoids. The incidence of colds was the same for all three groups. Both vitamin C groups had slightly leas severe colds than the placebo group. Thus the synthetic vitamin C was as effective as the natural vitamin C and the presence of bioflavonoids had no apparent effect [28]. Antihistamine Effect of Vitamin C

Histamine in varying amounts is almost always released in the tissues of the respiratory tract by an allergic-type response to the stress of common cold infections. Perhaps the first clue that animals and humans might use vitamin C to combat stress that involves histamine release came in 1940 from the research team led by the co-discoverer of vitamin C, Professor Charles Glen King of Columbia University. Dr. King's group showed that stressing rats with certain drugs stimulated their bodies to synthesize extra vitamin C [29]. Later, evidence was presented to support the belief that animals, such as the rat, who can make their own supply of vitamin C, react to histamine by producing extra vitamin C. In 1974, two other research teams found that rats given vitamin C along with histamine-releasing drugs had a reduction in stress symptoms and reduced histamine in the urine [30,31]. They concluded that vitamin C can act like an anti-histamine drug. However many physicians believe that reducing infection-caused inflammation (nature's defense reaction) slows recovery. Overview

In 1986, Professor A. Stewart Truswell of the University of Sydney, Australia concisely summarized the results of 27 trials conducted since 1970. [8] Of these, five were treatment trials with vitamin C or a placebo given only at the onset of a cold and for only several days and all of which found no benefit. The other 22 were double-blind controlled trials giving daily vitamin C or placebo before and during colds. Of these, 12 trials showed no prevention and no reduction in duration or severity, five trials showed no prevention and only slight, statistically nonsignificant lessening of severity, and the other five trials reported no prevention and a small but significant in reduction of duration of the colds. Dr. Truswell concluded: “It is now fairly clear that for preventing colds, vitamin C has no worthwhile effect,” but he believed that: “There is thus a little more evidence for a small therapeutic effect of ascorbic acid (vitamin C). However, as Dr. T.W. Anderson's second trial in 1974 revealed 250 mg of vitamin per day reduced severity as much as did 1,000 mg or 4, 000 mg [16].

Does it make sense to supplement with vitamin C? If so, should it be done daily or only at the first sign of a cold or other infection? And what dosage should be used? The many studies done in the last 30 years clearly prove that daily vitamin C supplements, whether 100 mg or 5,000 mg, do not prevent colds and provide, but only for some people, only a slight reduction in duration and severity of colds. Dr. Thomas Chalmers concluded in 1975: “I, who have colds as often and as severe as those of any man, do not consider the very minor potential benefit that might result from taking vitamin C three tines a day for life worth either the effort or the risk, no matter how slight the latter might be.” [5]

If you choose to supplement when a cold strikes, there is no reason to take more than 250 mg per day, as shown in the 1974 Anderson study. This amount is easily obtained from the age-old “remedy,” fruit juices. Supplementation with larger amounts of vitamin C has not been shown to be more effective, and it may cause diarrhea or have other adverse effects.

Editor's Note

Dr. Marshall, who died in 1997 at the age of 90, was a biochemist who devoted most of his retirment to investigating the benefits and risks of vitamin supplementation. His landmark book, Vitamins and Minerals: Help or Harm? won the American Medical Writers Association award for best book of 1983 for the general public and became a special publication of Consumer Reports Books. In 1992, Dr. Marshall revised the book's chapter on vitamin C and colds as a first step in developing a second edition, which, unfortunately, he was unable to complete. Upon his death, his family transferred his files and the rights to his writings to me with the understanding that I would use them for public education. This article was condensed from the revised chapter and will be updated when additional studies are done. References

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