Biochemical Individuality

Roger J. Williams and Linus Pauling, 1972

[Part 4 of 4 in a series on Vitamin C and the Common Cold]

Toward the end of his book Vitamin C and the Common Cold, Linus Pauling included a chapter on human biochemical individuality.  In it, he addressed the fact that every human is different, and as a result, each individual has a unique need for specific amounts of vitamin C.

Pauling pointed out that when any characteristic, such as the concentration of a certain enzyme in the red blood cells, is studied in a sample of 100 human beings, a wide range of values are invariably observed. The “normal” range is that in which 95 percent of those values lie, while the remaining 5 percent are described as abnormal. Defining normalcy on a larger scale is a bit tricky however. Pauling stated that

If we assume that 500 characters are independently inherited, then we can calculate that there is only a small chance, 10 percent, that one person in the whole population of the world would be normal with respect to each of these 500 characters.

The situation is complicated further by the fact that humans possess some 100,000 genes, each of which performs a different function.  “Accordingly,” Pauling wrote, “we reach the conclusion that no single human being on earth is normal (within the range that includes 95 percent of human beings) with respect to all characters.”

Guinea pigs, like humans, are also genetically heterogeneous, as was demonstrated in a 1967 vitamin C experiment carried out by Roger J. Williams and Gary Deason of the University of Texas, Austin. The investigators obtained more than 100 young male guinea pigs, and initiated their experiment by closely observing the guinea pigs for a week while they were fed a healthy diet. This completed, the animals were then divided into eight groups of 10 to 15 animals, with each group receiving varying amounts of ascorbic acid, and one group receiving none.

Each of the guinea pigs reacted differently to the amount of ascorbic acid given to them.  About 80 percent of the guinea pigs that were fed no ascorbic acid or less than 0.5 mg of ascorbic acid per kilogram of body weight per day showed signs of scurvy. Only a quarter of those receiving between 1 mg and 4 mg per kilogram per day showed signs of scurvy, while those receiving 8 mg per day or more did not show any signs of the disease. These results were in accordance with the commonly held belief that guinea pigs need about 5 mg per day of ascorbic acid in order to prevent scurvy.

However, the experiment also produced anomalies: two of the guinea pigs receiving only 1 mg of ascorbic acid per kilogram per day stayed healthy, and gained weight over the course of the eight-week experiment. One of them even gained more weight than any of the animals receiving a larger amount of vitamin C.

Strangely, seven of the animals receiving 8, 16, or 32 mg per kilogram per day were unhealthy, and did not grow very much. Five of these were then provided with 64 mg per kilogram per day, and two of them were provided with 128 mg per kilogram per day. When they were provided with larger amounts of vitamin C they began to grow at a much faster rate: initially, they had only grown about 12 grams in ten days, but during the next ten day cycle, while receiving more vitamin C, they gained an average of 72 grams each. The conclusion reached was that these seven guinea pigs, out of the thirty that were placed on between 8 mg and 32 mg per kilogram per day, possessed a larger built-in vitamin C requirement.

Williams and Deason determined that out of 100 guinea pigs, there existed a requirement range of at least 20 different levels of vitamin C. From there, the duo extrapolated that “the population of human beings is presumably not more uniform than that of guinea pigs used in their experiments, and that accordingly the individual variation in human vitamin C needs is probably just as great.”

Pauling agreed with this conclusion, adding that the requirement of ascorbic acid for humans probably ranges from 250 mg per day to 10 g per day. And he continued to make reference to biochemical individuality throughout the book, suggesting that 1 g to 2 g per day is approximately the correct amount of ascorbic acid for the average human being to ingest.

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Vitamin C Deficiency in Humans: An Issue of Evolution?

Linus Pauling and Irwin Stone, 1977.

[Part 3 of 4 in a series on Vitamin C and the Common Cold]

In the chapter “Vitamin C and Evolution” from his book Vitamin C and the Common Cold, Pauling wondered about the reasons why the rest of the animal world can synthesize vitamin C, while human beings, along with a very small group of mammals, cannot. His answer was gene mutation, using the instance of thiamine as evidence.

All animals need thiamine as an essential vitamin; in its absence they develop a disease similar to beriberi. Pauling theorized that over 500 million years ago, when the common ancestor to present-day birds and mammals lived, there existed an environment imbued with an abundance of green plants containing thiamine. By way of gene mutation, one of the animals living during that era must have lost the mechanism which allowed it to synthesize thiamine. This was advantageous to the animal – which was probably plant-eating – because it could obtain the thiamine it needed from the plants it ingested while simultaneously conserving the energy that it would have used to manufacture the vitamin.

Pauling pointed out that possessing this extra energy would have caused the animal to flourish and to have more offspring than others of its kind. The advantageous mutation would be passed on to certain of the progeny, who would in turn pass it on to their own offspring, and so on. Eventually the mutation would spread, and a few million years later all mammals and birds would possess the mutation.

Pauling believed that in the same way that all animals lost the biochemical machinery to produce thiamine, so too did human beings, primates, guinea pigs and a particular Indian fruit-eating bat lose the ability to synthesize vitamin C. A mutation that results in the inability to synthesize a substance is simple and occurs often; it only requires a single gene to be damaged or deleted. The reverse process is more complex and takes much longer. The mutation that removed the ability to synthesize vitamin C probably took place about 25 million years ago, in the ancestor of modern primates and humans.

In his book, Pauling next asked the question, why didn’t all mammals and birds lose the ability to synthesize vitamin C the way that they lost the ability to synthesize thiamine? Pauling theorized that the change likely occurred in the guinea pig and the Indian fruit-eating bat independently of the common precursor of the primates, due to an abundance of vitamin C in their diets. The fact that the majority of animals possess the ability to synthesize vitamin C indicates that there is not sufficient vitamin C in their dietary environment for them to obtain the vitamin solely from their nutrition intake.  To Pauling, this also suggested the existence of a deficiency of ascorbic acid in the human diet.

Dr. Irwin Stone, a biochemist in Staten Island, New York, was the person responsible for sparking Linus Pauling’s interest in vitamin C. Dr. Stone, a leader in the ascorbic acid field at the time, sent a letter to Pauling in 1966 informing him of a high-level ascorbic acid regimen that he had been developing over the past three decades, which Pauling and his wife began to follow. Stone believed that humans need between 3 and 5 grams of vitamin C per day, reinforcing this claim by citing the British researcher G. H. Bourne’s evidence that gorillas ingest about 4.5 g of ascorbic acid per day.

Gorillas, like humans, do not synthesize vitamin C, and so need to obtain it from their diet. In 1949 Bourne pointed out that before the development of agriculture, humans lived mainly off of raw, green plants with little meat; a diet similar to that of the modern gorilla. Bourne concluded that

it may be possible, therefore, that when we are arguing whether 7 or 30 mg of vitamin C a day is an adequate intake we may be very wide of the mark. Perhaps we should be arguing whether 1 g or 2 g a day is the correct amount.

Irwin Stone also took into consideration the amount of ascorbic acid that other animals, such as rats, manufacture. The rat synthesizes vitamin C at a rate of between 26 mg and 58 mg per day per kilogram of body weight. If the same rate of manufacture were applied to humans, a person weighing 70 kg (154 lbs) would need to ingest between 1.8 g and 4.1 g of ascorbic acid per day.

From there, Pauling verified the amounts of various vitamins contained in 110 different raw fruits and vegetables corresponding to a diet of 2,500 kilocalories per day, and found that “for most vitamins this amount is about three times the daily allowance recommended by the Food and Nutrition Board.” For ascorbic acid, the difference was much more drastic: the average amount of ascorbic acid in a day’s ration of the 110 raw foods was 2.3 g, which was about 42 times the recommended amount. Pauling argued that

If the need for ascorbic acid were really as small as the daily allowance recommended by the Food and Nutrition Board the mutation would surely have occurred 500 million years ago, and dogs, cows, pigs, horses, and other animals would be obtaining ascorbic acid from their food, instead of manufacturing it in their own liver cells.

Pauling found that the average ascorbic acid content for the fourteen most vitamin C-rich plant foods is 9.4 g per 2,500 kilocalories, leading him to the conclusion that the optimum daily vitamin C intake for an adult human being is between 2.3 g and 9 g – quantities in line with what he saw as existing in the natural diet of the human lineage and numbers far beyond the recommendations issued government nutritional authorities, then or now.

Physicians Anecdotes and the Safety of Large Doses

[Part 2 of 4 in a series on Vitamin C and the Common Cold]

“The medical profession itself took a very narrow and very wrong view.  Lack of ascorbic acid caused scurvy, so if there was no scurvy there was no lack of ascorbic acid.  Nothing could be clearer than this.  The only trouble was that scurvy is not a first symptom of lack but a final collapse, a premortal syndrome and there is a very wide gap between scurvy and full health.”

-Albert Szent-Gyorgyi

In writing his book Vitamin C and the Common Cold, one of Linus Pauling’s primary aims was to convince the general public of the safety and effectiveness of ingesting vitamin C in large doses. Early on in his text, Pauling stated that “an intake of about 10 mg per day is enough to provide protection against scurvy for most people, but to achieve the best health a much larger intake is probably needed.” The exact amount of vitamin C needed for optimum health is not known, since each person has a different requirement, but Pauling proposed that most people need between 250 mg and 10 g daily.

The range that Pauling prescribed was much higher than was the daily allowance recommended, at the time, by the Food and Nutrition Board of the National Research Council. In 1970, at the time that Vitamin C and the Common Cold was published, the Board was advising a healthy daily allowance of vitamin C of 35 mg for infants, 40 mg for children, 55 mg for women and 60 mg for men – amounts which were somewhat higher than the minimum 10 mg necessary to prevent scurvy, as calibrated to allow for individual variability and for potential losses in food. The current Recommended Daily Allowance for vitamin C is similar to that of the 1970s for infants and children, but has increased to 90 mg for men and 75 mg for women.

In his counterargument to the RDA, Pauling stressed that vitamin C is totally harmless, noting that guinea pigs given 0.5% of their body weight of vitamin C every day for a few days showed no adverse symptoms. He also noted that human subjects were known to have consumed as much as 40 g per day for a month without negative side effects. In fact, negative side effects seemed only to occur when a large amount of vitamin C was taken on an empty stomach.  As Pauling put it

A large amount (several grams) of ascorbic acid eaten without other food may cause an upset stomach and diarrhea in some people (hence the recommendation in Chapter 10 that it usually be taken at the end of a meal) but more serious side effects have not been reported.

Indeed, vitamin C is regarded to be as non-toxic as most cooking ingredients – no deaths or serious illnesses, Pauling wrote, have been attributed to it’s ingestion. Vitamin C is present in many fruits and vegetables, such as green peppers, red peppers, parsley, and turnip greens, as well as orange juice, lemon juice, lime juice, grapefruit juice, and tomato juice. Pauling noted, however, that cooked vegetables lose about half of their vitamin content, and as such should be cooked for the minimum amount of time and with a minimum amount of water.

Physicians Anecdote: Irwin Stone

Having made his case that vitamin C is totally harmless even in large amounts, Pauling moved on to include a few anecdotes from physicians who had personally benefited from a specialized ascorbic acid regimen. The influential Dr. Irwin Stone, a biochemist from Staten Island, New York, wrote in 1966 that he had ingested 3 g to 5 g of ascorbic acid per day for ten years. During this time he observed that he had not suffered a single cold. Stone’s recommended procedure for warding off the common cold was to take 1.5 g of vitamin C at the first sign of symptoms, and another 1.5 g again every hour. Stone’s experience suggested that the cold was usually eradicated by the time the third dose had been taken.

Edmé Régnier

Another physician, Edmé Régnier of Salem, Massachusetts, reported in 1968 that he had also found large doses of ascorbic acid to be useful in the prevention of the common cold. Régnier had suffered from chronic bouts of middle ear infection from the age of seven, an affliction for which he was unable to find a remedy and which led to his interest in vitamin C. Finally, after twenty years and several trials involving bioflavonoids and ascorbic acid, he found that “the serious and disagreeable manifestations of the common cold and the accompanying inflammation of the middle ear could be averted by the use of large amounts of ascorbic acid.” Régnier studied 22 subjects, giving them either ascorbic acid alone, ascorbic acid plus bioflavonoids, only bioflavonoids, or a placebo, over the course of five years. The subjects were not told which preparation they were receiving, but eventually one subject realized that he was not receiving the ascorbic acid that could have prevented his developing a cold.

Edmé Régnier

Régnier recommended the administration of 600 mg of ascorbic acid at the first manifestations of a cold, a quantity quite a bit lower than Stone’s recommendation of 1.5 g.  Régnier likewise suggested that the initial dose should be augmented by 600 mg of ascorbic acid every three hours, or 200 mg every hour, ending with a dose of 750 mg just before bedtime. This regimen, Régnier argued, should be continued for three or four days, decreasing to 400 mg every three hours, and then to 200 mg every three hours. According to Régnier’s study, 31 out of 34 colds were averted using ascorbic acid plus bioflavonoids, and 45 out of 50 colds were averted using only ascorbic acid. Neither bioflavonoids alone nor the placebo were effective. He cautioned, however, that if the ingestion of ascorbic acid were to be suddenly discontinued, a cold may resurface again, even if a week or more has passed by.

Douglas Gildersleeve

In the July-August 1967 issue of Fact magazine, Douglas Gildersleeve, M.D., added a somewhat conspiratorial tone to the conversation in his article “Why Organized Medicine Sneezes at the Common Cold.” In it, Gildersleeve stated that ascorbic acid, an “effective treatment” for the common cold, was being ignored because it would adversely affect “pharmaceutical manufacturers, professional journals, and doctors themselves.”

Gildersleeve studied more than 400 colds in 25 subjects, mostly his own patients, giving them about 4 g of ascorbic acid per day. He reported that the ascorbic acid was effective in 95 percent of his patients, eliminating completely the most common symptom – excessive nasal discharge – while drastically reducing other symptoms of a cold. None of his patients suffered negative side effects. Gildersleeve wrote a paper in 1964 detailing his observations, and submitted it to eleven different professional journals. Every single one rejected it. According to Gildersleeve, one editor told him that medical journals depended on the support of advertisements, over twenty-five percent of which were related to drugs for symptoms of the common cold or complications of colds. This same editor allegedly told him that it would be “harmful to the journal to publish a useful treatment for the common cold.”  And so it was that Gildersleeve’s data went unpublished until the Fact article three years later.

Five Controlled Trials

[Part 1 of 4 in a series on Vitamin C and the Common Cold]

Linus Pauling became interested in ascorbic acid thanks to Dr. Irwin Stone, a biochemist from New York. After meeting Pauling in 1966 and hearing Pauling speak of his desire to live for an additional fifteen or twenty years, Dr. Stone sent him his own high-dose ascorbic acid regimen, which Pauling and his wife Ava Helen soon began to follow. After adhering to this program for several years, the Paulings observed a shared feeling of increased well-being and a striking decrease in the number of colds that they were contracting.

Linus Pauling was convinced that vitamin C was powerful enough to cure the common cold, but he was also aware that many authorities did not share his opinion.  He addressed this conflict in Chapter Five of his book Vitamin C and the Common Cold (1970) noting his desire to

resolve the apparent contradiction between the opinions expressed by authorities in nutrition and my own experience, which supported the widely held belief that ascorbic acid has value in decreasing the incidence of infection and ameliorating the severity of the common cold.

Pauling argued that ascorbic acid provides a minimal amount of protection against colds when taken in small amounts, but that the effect is proportionately greater when it is taken in much larger doses. According to Pauling, protection against colds becomes “nearly complete” when, shortly after the onset of a cold, one ingests four to ten grams of ascorbic acid per day. In support of his argument, Pauling cited five controlled trials conducted with various groups of people around the world.  These trials, he felt, supported his idea that health can be improved by adding more vitamin C to one’s diet.

Cowan, Diehl and Baker, 1942

The first study Pauling listed was an analysis of about 400 students at the University of Minnesota, conducted by Cowan, Diehl, and Baker during the winter of 1939-1940, and published in 1942 in the Journal of the American Medical Association. In this study, for twenty-eight weeks about half of the Minnesota students received 100 milligram tablets of vitamin C twice per day, while the other half received a placebo. The investigators concluded that the young adults who were already on a healthy diet were not greatly influenced by the 200 mg of vitamin C per day.  However, the study also yielded other important results.

First, the group receiving ascorbic acid throughout the twenty-eight week period experienced an average of 1.9 colds per person, with a 0.07 cold margin of error. Meanwhile, those in the placebo group reported an average of 2.2 colds per person, with a 0.08 margin of error. The investigators concluded that

the actual difference between the two groups during the year of the study amounts to 1/3 of a cold per person…[o]ne may therefore consider this as probably a significant difference, and vitamin C supplements to the diet may therefore be judged to give a slight advantage in reducing the number of colds experienced.

Pauling pointed out that this amounted to a 15% decrease in the quantity of colds per person. And although the investigators seemed to judge this a bordering-on-negligible amount, Pauling thought differently, wondering in his text if increasing the dosage to 400 mg of ascorbic acid per day would have decreased the colds twofold.

Another point in the Minnesota data that Pauling found compelling was the fact that of the 233 students participating in the ascorbic acid group, only 25 dropped out over the course of the study.  On the other hand, 39 students dropped out of the control group, which had started with 194 participants. Pauling drew the conclusion that a greater percentage of the students receiving ascorbic acid felt that they were benefiting from the study. Pauling likewise noted that the group which received vitamin C only missed an average of 1.1 days of school over the twenty-eight week study, while those who received the placebo lost an average of 1.6 school days.

Glazebrook and Thomson, 1942

In 1942 Glazebrook and Thomson published a similar study in the Journal of Hygiene, though this one focused on an institution of about 1,500 students in Scotland, where the students ranged in age from 15 to 20 years old. Glazebrook and Thomson’s group consumed a total dietary intake of only about 5 to 15 mg of ascorbic acid per student per day. This number was so low mainly because the school’s food was kept hot for two hours or more before serving, a practice which caused the served vegetables to lose much of their vitamin content.

In the Scottish survey, 335 students were given extra ascorbic acid – 200 mg per day for six months – while the remaining 1,100 served as a control. The ascorbic acid group recorded a 30.1 percent incidence of colds and tonsillitis, while the control group reported a 34.5 percent incidence. From these results, Pauling extrapolated that among the students who were given ascorbic acid, there were 13 percent fewer colds – a number close to the 15 percent decrease found in the Minnesota study.

The Scottish students who displayed more severe symptoms of colds or tonsillitis were admitted to Sick Quarters – 23.0 percent of the ascorbic acid group compared to 30.5 percent of the control group. This meant that 25 percent fewer students in the ascorbic acid group were admitted to Sick Quarters than were those in the control group.

Likewise, those receiving vitamin C also managed to stay out of the hospital: the average number of days spent in hospital due to infection for the control group was 5, versus 2.5 for the ascorbic acid group.  Drilling even deeper, there were 17 cases of pneumonia and 16 cases of acute rheumatism reported among the controls, while neither illness showed up in the ascorbic acid group.  Pauling used this data to emphasize the power of ascorbic acid in countering serious infections as well as the common cold.

Linus Pauling at an international vitamin symposium, Sao Paulo, Brazil, 1980.

Franz, Sands and Heyl, 1956

From there, Pauling briefly recounted an observation of 89 volunteer medical students and student nurses whose health was tracked for three months. The paper that resulted was published in a 1956 issue of the Journal of the American Medical Association by Franz, Sands, and Heyl. The study was constructed such that 44 of the students received 195 mg of ascorbic acid per day, while the remaining 45 received none.  In this instance, students in both groups experienced about the same number of colds, but the colds were judged to be less severe for the ascorbic acid group. It was concluded that this decreased severity and rapid improvement was “statistically significant at the 0.05 level.”

Wilson and Low, 1970

While each of the above studies and their results were relevant to Pauling’s case, Wilson and Low’s 1970 Acta Allergologica paper was of greater importance because it was a double-blind investigation. In this instance, neither the subjects – 103 students at a girls’ school in Ireland – nor the investigators evaluating the effects of the preparation knew which subjects had been given the placebo and which ones had been given vitamin C; that is, not until the study had reached its conclusion. As with the previous trials, the amount of 200 mg per day was used, but in the Wilson-Low group, 57 students received ascorbic acid while 46 received a placebo tablet over a period of three winter months.

Wilson and Low’s data indicated that ascorbic acid “reduced the incidence, duration, and severity of the symptoms of both toxic colds (sore throat, headache, fever, malaise) and catarrhal colds (cold in the head, cough, nasal obstruction, nasal discharge).” Symptoms of catarrhal colds lasted 8 days for the ascorbic acid group as opposed to 14 in the placebo group.

Pauling also noted that laboratory work indicated that the girls receiving ascorbic acid showed a higher concentration of ascorbic acid in the white blood cells than did the control group: the girls who had been receiving 200 mg of ascorbic acid once a day for 6 months had, on average, 60 micrograms of ascorbic acid present per hundred million cells, while those in the control group averaged 43 micrograms per hundred million cells. Pauling believed that “[t]his increase may be in part responsible for the increased resistance to infection.”

Ritzel, 1961

While these four studies seemed to show that about 200 mg of vitamin C daily can lessen the duration and symptoms of the common cold, Pauling needed to reinforce his hypothesis that “a somewhat larger intake of ascorbic acid provides somewhat greater protection.” To do so, Pauling turned to another double-blind study carried out in 1961 by the Swiss investigator Gunther Ritzel and published in Helvetica Medica Acta.

Unlike the rest of the literature cited by Pauling, Ritzel used 1000 mg of ascorbic acid, and noted a much greater effect than did the previous 200 mg studies. In his test of 279 skiers, Ritzel provided half of the subjects with 1000 mg of ascorbic acid per day, while the other half received a placebo. Among the vitamin C group, the data indicated a reduction of 61 percent in the number of days of illness from upper respiratory infections, and a 65 percent decrease in individual symptoms. Pauling was quick to note the substantial improvement in Ritzel’s group as compared to the 15 percent decrease brought about in the earlier studies by the daily ingestion of 200 mg of vitamin C. The data all seemed to provide solid evidence for Pauling’s basic rule of thumb:  when it comes to the common cold, the more vitamin C the better.

Vitamin C, the Common Cold and Controversy

By Tom Hager

[Part 3 of 3. For the full text of this article, originally presented as a lecture sponsored by Oregon Health Sciences University, please see this page, available at http://thomashager.net]

Portuguese edition of Vitamin C and the Common Cold, a book that was translated into nine different languages.

Pauling’s reading of the literature convinced him that the more vitamin C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got.  It was at this point that Pauling made what I consider to be a fundamental mistake. He decided to publish his ideas without peer review, in the form of a popular book.

He did not feel he could wait. He had, he thought, good evidence that a cheap, apparently safe, easily available nutrient could prevent at least an appreciable fraction of a population from suffering through an affliction that made millions of people miserable. And there might be even greater results. Pauling had read of small villages, snowbound in the winter, where no one got colds because there was no reservoir of respiratory viruses to pass around. When visitors arrived in the spring, they would bring colds with them, and everyone would suffer. What if, through the use of vitamin C, a great many more people strengthened their resistance to colds? The two hundred or so cold viruses rampant in the world would have many fewer places to replicate themselves. The spread of colds would lessen; the population of cold viruses would decrease. “If the incidence of colds could be reduced enough throughout the world,” Pauling thought, “the common cold would dis­appear, as smallpox has in the British Isles. I foresee the achievement of this goal, perhaps within a decade or two, for some parts of the world.” Vitamin C, properly and widely used, might mean the end of the common cold.

Packaging for commercial cold remedies pasted by Pauling into his research notebook, July 1970.

This, of course, would not only greatly lessen the amount of suffer­ing in the world; it would increase the fame of Linus Pauling. He was nearing seventy years of age. It had been nearly twenty years since he had captured international attention for his scientific work with proteins, and won the Nobel Prize for chemistry. His efforts had gone to politics in the years since, and none of his recent scientific work had had much impact. Science was moving on without him. He was becoming a historical figure.

Pauling did not feel like one. He was not ready for emeritus status, trotted out at honorary occasions, shunted aside while the young men made the discoveries. He was still strong, still smart, still a fighter. Or­thomolecular medicine was the newest of his grand plans, and no one had shown that his ideas about creating an optimal molecular environ­ment for the body and mind were wrong. The evidence he had uncov­ered about ascorbic acid and colds, evidence that showed human health could be improved by increasing the amount of vitamin C in the body, was the strongest indication yet that he was right. Bringing it to the public’s attention would not only be good for the public; it would be a striking example of the correctness of his general theory.

Pauling’s book Vitamin C and the Common Cold, written in his usual clear, well-organized, straightforward style, presented the results of his literature search. He discussed the findings of five controlled trials that supported his idea, several anecdotal instances of physicians who had treated colds with vitamin C, and evidence that ascorbic acid was safe in large doses. Pauling felt confident that a several-gram daily dose would do no more harm than to cause loose stools, that vitamin C was safe, especially compared with potentially toxic, commonly avail­able over-the-counter medications such as aspirin. The rest of the book was a summary of his orthomolecular thinking and Irwin Stone’s ideas about evolution. A good deal of space was devoted to the topic of bio­chemical individuality, which resulted in a wide personal variation in the need for vitamin C and other nutrients.

On November 18, 1970, prepublication galleys were released to the press, and an unprecedented public roller-coaster ride began. The next day, the New York Times quoted Pauling as saying that humans needed between 1 and 4 grams of vitamin C per day to achieve optimal health and prevent colds. Pauling also took the occasion to slam the medical establishment – from drug companies to medical journals and physicians – for attempting to quash the evidence in favor of ascorbic acid. Why would they do that? the reporter asked. Look at the cold-remedy industry, Pauling said: It was worth $50 million per year, and that bought a lot of advertising space in medical magazines.

This quickly alienated both physicians and the editors of medical journals, neither of whom liked the implication that profits were more important than health. The medical establishment felt it necessary to respond, and respond quickly, once they saw how Pauling’s idea took off.

The book sold wildly, and so did vitamin C.  Pauling’s timing, at least on the public side, was superb. The 1960s had seen a resurgence of interest in “natural” health based on a holistic attitude that said body, mind, and soul were one. Many streams fed into this alternative health movement: a back-to-the-land, organic-foods orientation; a fas­cination with yoga, acupuncture, meditation, and other Eastern health practices; the rediscovery of the lost Western arts of naturopathy and homeopathy. Pauling’s message about vitamin C resonated with mil­lions of people who were reacting against corporate, reductionistic, paternalistic medicine, with its reliance on drug therapy, with people taking a renewed responsibility for their own health and trying to do it naturally. It was delivered just as natural food stores were popping up on corners in every town in America, each one stocked with a section for herbal remedies, a rack for magazines on alternative health regi­mens, and plenty of shelf space for vitamins.

The publication of Pauling’s book triggered a nationwide run on vitamin C. Sales skyrocketed, doubling, tripling, quadrupling, within a week of its appearance. Druggists interviewed in newspapers across the nation told of people coming in to buy all the vitamin C they had. Wholesale stocks were depleted. “The demand for ascorbic acid has now reached the point where it is taxing production capacity,” said a drug company spokesman less than a month after Pauling’s book ap­peared, adding, “It wouldn’t pay to increase production capacity since we’re sure it’s just a passing fad.”

The reaction was swift. The physician-head of the Food and Drug Administration (FDA), Charles C. Edwards, announced to the press that the national run on vitamin C was “ridiculous” and that “there is no scientific evidence and never have been any meaningful studies in­dicating that vitamin C is capable of preventing or curing colds.” The FDA, Pauling found, had proposed in 1966 that no vitamin C tablets over 100 mg be available without a prescription, and he responded to Edwards with sarcasm. If the FDA had its way and he wanted to take 10 grams of vitamin C to fight off a cold without going to a physician for a prescription, Pauling said, he would have to take 100 tablets. “I think I would have as much trouble swallowing all these tablets as I would swallowing some of the statements made by the Food and Drug Ad­ministration in proposing these regulations,” he said.

The medical press was equally critical of Pauling. The American Journal of Public Health said that Pauling’s book was “little more than theoretical speculation.” The Journal of the American Medical Association said of Pauling’s book, “Here are found, not the guarded statements of a philosopher or scientist seeking truths, but the clear, incisive sentences of an advertiser with something to sell. . . . The many admirers of Linus Pauling will wish he had not written this book.” The Medical Letter launched the harshest attack yet, saying Pauling’s conclusions “are derived from uncontrolled or inadequately controlled clinical studies, and from personal experience” and pointing out that there was no good evidence that vitamin C was safe when taken over a long period of time in large doses.

The controversy over Pauling’s book arose from a simple fact: He had not made his case. The book was a combination of his interesting but unproven speculations about orthomolecular medicine and the human evolutionary need for ascorbic acid, coupled with a select handful of studies that indicated that vitamin C could prevent or ame­liorate colds in a fraction of a population. That might make an inter­esting conference paper, but it was little reason to advocate a wholesale change in the dietary habits of a nation. His critics pointed out that he had no clear theory of how vitamin C exerted it powers and that there was no good study – no study at all – establishing that the long-term ingestion of megadoses of vitamin C was safe. The current dogma in the medical profession was that vitamins were needed only in the small amounts provided by a well-balanced diet. Taking grams of vitamin C every day might cause everything from gastric upset to kid­ney stones, and who knew what else?

The way he had gone about publicizing his ideas, sidestepping the normal channels of scientific peer review to publish a popular book, also fueled criticism. He was behaving like a health faddist, not a scien­tist. In the eyes of most physicians – generally conservative about new therapies, disdainful of the holistic health movement, trained to be­lieve that vitamin C was needed only to prevent scurvy – Pauling looked like a nutritional quack, a vitamin pusher who was essentially prescribing without a license.

Typically, Pauling fought back. To pursue his ideas, in 1973 he cofounded (with Arthur Robinson, a young colleague who later moved to Oregon and this year ran for Congress) the Institute of Orthomolecular Medicine in Palo Alto, California.

He went on to publish more books, adding the flu as another disease vitamin C could fight, then Vitamin C and Cancer, and finally compiled all his ideas into How to Live Longer and Feel Better.

Anecdote published in Chemtech, September 1994.

Criticism from the medical community has never let up. A general belief still exists in most – although not all – of the medical community that Pauling went off his rocker.

However, despite what many physicians believe, the jury is still out. A significant amount of active biomedical research research continues to examine the effects of micronutrients on a variety of conditions. For instance the Linus Pauling Institute at Oregon State University (successor to Pauling’s Orthomolecular Institute) maintains a highly successful research program in 12 laboratories funded with millions of dollars of competitive grant funding. The Institute’s head, Balz Frei, believes that Pauling’s basic approach remains sound – but that his arguments with physicians might have caused as much damage to the study of nutritional science as they did good. In my own view, by putting personal controversy ahead of reasoned consensus both Pauling and his critics polarized the public into groups that still have trouble communicating with each other.

Pauling’s work helped give birth to today’s booming market in nutritional supplements. Vitamin C remains the world’s largest-selling supplement. A large number of advocates strongly believe that ingesting vitamins in amounts far above the RDA can help optimize human health, especially by preventing chronic disease. There is a growing understanding that the key in these studies – as Pauling pointed out long ago – is not to look for vitamins to act like pharmaceuticals, exerting significant effects at low doses, but more like nutrients, with less dramatic effects that accumulate at much higher doses.

Linus Pauling himself lived an active life well into his nineties, performing useful research until the end. He was taking many grams of Vitamin C every day.

Will the controversy he started ever end? Was he a genius, or a crank?