Evolution and the Need for Ascorbic Acid

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Linus Pauling, 1970

Linus Pauling’s belief in the value of vitamin C emerged from many sources, but key among them was the fact that humans, for most of their history, have been unable to produce their own ascorbic acid. This stands in stark contrast to nearly every other animal, virtually all of whom are able to synthesize their own ascorbic acid internally. Pauling viewed this human characteristic as having emerged from an evolutionary adaptation that, in his view, had sentenced modern humans to lives of sub-optimal health.

In December 1970, Pauling detailed this point of view in an article titled “Evolution and the Need for Ascorbic Acid,” which was published in the Proceedings of the National Academy of Sciences. In it, Pauling began by stating that the minimum daily requirements then espoused for vitamin C – 35 mg for an infant and 60 mg for an adult – were only enough to stave off scurvy and remained grossly insufficient to supporting ideal human functioning. In so doing, Pauling framed the onset of scurvy as not just the first symptom of low ascorbic acid levels, but rather the last symptom before death.

Pauling then pointed out that, along with the guinea pig, the Indian fruit-eating bat, and an early ancestor of the Passeriformes bird, humans are among a tiny minority of the world’s animals who are incapable of synthesizing their own ascorbic acid. The question is, why?


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Table 1 (excerpted) from Pauling’s 1970s PNAS article.

Pauling took an evolutionary view as he searched for an answer. In his article, he began by defining the eobiontic period – a two to three billion year period after the “hot thin soup” era – as a phase characterized by profound biochemical evolution. It was during this time period, about 25 million years ago, where Pauling believed that humans lost the ability to self-produce ascorbic acid.

To demonstrate how this might have happened, Pauling detailed a similar circumstance with thiamine, which is also an essential nutrient for mammals. At some point during the eobiontic period, certain species also began to lose their ability to synthesize thiamine and many researchers, including Pauling, believed that this was because “the supply of food available to an earlier ancestor provided an adequate supply of these vitamins, enough to make it advantageous to discard the mechanism for synthesizing them.” According to the theory, those species that did not discard this mechanism were disadvantaged because maintaining synthetic production became a burden. “[I]t cluttered up the cells,” Pauling wrote, “added to the body weight, and used energy that could be better used for other purposes.”

Pauling believed that the abundant availability of foods rich in vitamin C also led humans to evolve away from synthesizing ascorbic acid. Pauling listed 110 of these foods in a table within his article. They included sweet red peppers, sweet green peppers, hot red chili peppers, parsley, black currants, and broccoli spears among many others.


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Irwin Stone. (Image by Oscar Falconi)

Pauling also examined the research of three colleagues to add support for his theory: British researcher G.H. Bourne, American biochemist Irwin Stone, and American physician Edmé Régnier. Pauling looked to these three in particular to try and calibrate the level of ascorbic acid intake that would result in ideal human functioning.

In 1949, G.H. Bourne conducted a study focusing on the diets of gorillas and found that they consumed nearly 4.5 g of ascorbic acid per day through green foods. The variety of foods consumed by gorillas was also deemed by Bourne to be similar to that likely consumed by humans prior to the development of agriculture. By comparing the diets of the two, as well as their proportional body weights, Bourne determined that contemporary humans should strive to consume closer to 1 or 2 grams of ascorbic acid per day, rather than the the 7 to 30 mg recommended at the time.

Later, in the mid-1960s, Irwin Stone performed a set of experiments with a similar aim. After discovering that the daily rate of vitamin C synthesis for rats ranged from 26 mg kg-1 to 58 mg kg-1, Stone determined that the best intake of ascorbic acid for optimum human health was between 1.8 g to 4.1 g per day – the levels that individuals of varying sizes would produce if the rat synthesis rate were scaled accordingly.

Only a couple years after Stone released his hypothesis, Edmé Régnier produced his own theory that settled on a regiment of 5 g of ascorbic acid per day. Further, after several trials in which Régnier administered varying amounts of ascorbic acid to study participants, Régnier concluded that 45 out of 50 colds had been prevented by doses of 600 mg of ascorbic acid. Not long after, Pauling would write a book that did much to popularize the use of vitamin C in the treatment and prevention of the common cold.


After considering the research of the previous three scientists as well as conducting trials of his own, Pauling theorized that optimal human intake of ascorbic acid likely ranged from 2.3 g to 9.5 g. Pauling’s minimum recommendation was 2.3 g because that was the average amount of ascorbic acid provided by the 110 natural foods listed in his table. Likewise, Pauling deduced that the amount required to achieve optimal health would not exceed 9.5 g, because that was the high-end total available through a smaller selection of foods described in the same table.

Pauling also recognized the importance of biochemical individuality, age, size, and gender, and considered all of these factors in publishing his 2.3 g to 9.5 g range. He likewise took comfort in knowing that his conclusions were similar to those of Stone and Bourne, and this corpus of research convinced Pauling, for the remainder of his life, that vitamin C was an essential key to achieving optimal health.

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.