Continuing Work on Vitamin C and Cancer: An Interview with Matthew Kaiser

Matthew Kaiser.

Matthew Kaiser.

The blog recently had the opportunity to sit down with Matthew Kaiser, an Oregon State University undergraduate senior in microbiology from Salem, Oregon.  Kaiser, who hopes to pursue a career as an MD/Ph.D., has led an exciting research project on the potential treatment of cancer using intravenous vitamin C.  He also recently delivered a talk titled “Is Humanity Ready for an Upgrade?” at a recent TEDx symposium hosted by OSU.

What follows below is an edited excerpt of our interview with Kaiser in which he discusses the roots of his project, its potential application, and his experience of conducting and presenting high level research at a very young age.

The Roots of the Research Project 

The beginnings of this research project were more or less like most undergraduate project tend to start. Not all, but some tend to be these big black box projects, we call them, in that there are a lot of unknowns. It’s almost like, “we really don’t know a lot about this but hey, we’ll give it to an undergraduate to take a stab at it. Because even that way if it doesn’t work out, if we find out that there really is no story here, they get the research experience and then we don’t necessarily waste a graduate student’s time or post-doc’s time on a project that didn’t end up being published.”

But where this project started was, of course, back in the days of Linus Pauling who was among the first to suggest that high doses of Vitamin C could have an anti-cancer effect. But following his initial studies with Vitamin C, or ascorbate, there were studies that came out by the Mayo Clinic and other labs that showed that Vitamin C did not have a protective or anticancer effect. And so it was largely abandoned by the medical community for several years but it continued to be researched in kind of an alternative medicine environment. Through that, as our understanding of how Vitamin C is metabolized by the body developed, we were able to understand that if Vitamin C was delivered orally, it was completely different than how Vitamin C could be regulated if it was administered through an IV, because if you administer it through an IV you’re able to bypass all the digestive control and renal reabsorption in your small intestine. That normally would limit the amount of Vitamin C that gets into your bloodstream and then becomes vitally available.

So this project started kind of on the cusp of these exciting studies looking at the pharmacokinetics and, again, looking at the bioavailability of Vitamin C. And just to put it in perspective: so if you go home and eat fifty oranges, like all my friends like to try and do because they know I work on Vitamin C, they’re like “oh, Vitamin C and cancer, I can eat fifty oranges, right? And I can prevent cancer or cure myself or colon cancer?” And what we’re looking at in this project are doses that can only be achieved by IV because if you eat these fifty oranges, the maximum you can saturate your blood plasma level is about 220 micromolar. To put it in perspective, so if you can saturate your blood to a level of about 200 micromolar following oral ascorbate, if you go home and had an IV or you went to a clinic and you had an infusion of IV ascorbate, you can saturate blood plasma up to 30 millimolar. And there’s a thousand micromolars in one millimolar. So, extremely different doses can be achieved by these two different routes.

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Irwin Stone’s Impact on Pauling

Linus Pauling and Irwin Stone, 1977.

Linus Pauling and Irwin Stone, 1977.

[Part 2 of 2]

Four years after Irwin Stone first convinced Linus Pauling to start taking megadoses of vitamin C, Pauling decided to share with the world the successes that he had observed in his own improved mental and physical health.

In 1970 Pauling began to work on a book, Vitamin C and the Common Cold, and he wrote to Stone asking permission to dedicate it to him. He also sent Stone a copy of the manuscript to review. Stone wrote back praising the work.

The book is excellent and should go far to eliminate this thoroughly unnecessary and annoying condition, at least among your readers. The audience will increase over the years, especially if Medicine can eventually see the light.

Stone continued to encounter difficulty getting his own scientific articles about ascorbic acid published and he certainly did not have the funding to run his own clinical trials. Partly as a result, he too was writing a book about vitamin C and all of the many diseases that he thought were related to hypoascorbemia. A  major thrust of the book was its plea for large scale research on the topic. Stone hoped to get popular opinion on board with his ideas in order to place pressure on physicians and nutritionists to do research in this area.

Pauling’s Vitamin C and the Common Cold was a popular success. Many readers around the world were persuaded by his ideas and began to take vitamin C supplements to prevent and treat colds. Some of his acclaim rubbed off on Irwin Stone, who wrote to Pauling telling him that he too was finally receiving recognition from popular media sources, including NBC.

In 1971 Stone retired to San Jose, California and devoted the rest of his life to researching and promoting the need for high consumption of vitamin C by humans. That same year he finished his book, The Healing Factor: Vitamin C Against Disease, and asked that Pauling write a foreword for it. Pauling was glad to do so, calling it “an outstanding contribution to knowledge.”

Stone's inscription to Pauling in a first edition of The Healing Factor, 1972.

Stone’s inscription to Pauling in a first edition of The Healing Factor, 1972.

Despite their popular appeal, Pauling and Stone continued to encounter problems convincing medical practitioners and researchers to take their ideas about ascorbic acid seriously. Stone believed that this was so because vitamin C would be a much more inexpensive cure than the current treatments of the time, causing pharmaceutical companies and doctors to lose money.

One medical doctor, Ewan Cameron, did believe in the effectiveness of vitamin C against cancer and was treating his terminal cancer patients with megadoses of it in Glasgow, Scotland. He formed a trans-Atlantic research partnership with Pauling in 1971 and they began to collaborate on papers discussing the use of vitamin C against cancer, eventually publishing ten articles together.

Through his partnership with Pauling, Cameron also began to correspond with Stone about the implementation of vitamin C against cancer and their shared difficulties getting the medical community to accept their hypotheses.

Cameron maintained a unique viewpoint on the treatment of cancer and how ascorbic acid might fit into a clinical regimen. In December 1974, he explained his views to Stone.

It is completely contrary to all contemporary medical thought to even suggest that such a mundane substance as ascorbic acid could have any value in such a complicated disease as cancer. This is because cancer research is concentrating all its energies in searching for more and more sophisticated ways of selectively destroying cancer cells. The research is becoming so complex and so unproductive, that it is natural to assume that ‘the answer’ must be extraordinarily complex and almost beyond human comprehension….We would make much more progress if we accept that cancer cells are normal cells that merely happen to be behaving in an abnormal way. We would then accept that cancer cells have an equal right to live, and concentrate our energies in suppressing the abnormal behavior pattern.

Throughout their correspondence, Cameron described his successes treating cancer with ascorbic acid. But he also noted that a number of patients showed no improvement from it or, at best, their cancer was brought to a standstill. He was disappointed that his primary successes were mostly by way of increasing patients’ survival time, not in curing them. Cameron thought that the greatest success would be in prophylaxis – taking megadoses of ascorbic acid throughout one’s life in order to prevent cancer.


In 1978 Stone wrote a letter to the editor of Nutrition Today in response to the publication’s recent issue focusing on ascorbic acid. His letter shows how fervently he believed in hypoascorbemia.

I regard our most serious medical problem to be the dangerous complacency that the orthodox medical establishment exhibits toward Chronic Subclinical Scurvy and its refusal to do anything to correct and alleviate this potentially-fatal human birth defect. Chronic Subclinical Scurvy has killed more human victims, caused more disease and misery among Mankind than any other single factor in the past and is continuing this evil record in the present. I’m worried about the future, because that is where I’m spending the rest of my life.

Meanwhile, Stone and Pauling’s relationship continued to flourish. In 1977 Pauling invited Stone to become a member of the Board of Associates of the Linus Pauling Institute of Science, an offer that was accepted. Pauling also attended Stone’s surprise 70th birthday party that year. In 1981 Stone was unable to make it to Pauling’s 80th birthday, but he did pass along a message.

You will recall the promise I made you in 1966 of 50 more healthy years of life with Megascorbics. You thought I was exaggerating and said you would be satisfied with 15 years. Well the 15th year is now and I am looking forward to attending your 115th birthday party in 2016. Megascorbics makes you practically indestructible.

In response, Pauling wrote, “I am glad to express my thanks to you for having written to me in 1966. Your letter and the reprints of your papers changed my life.” While Pauling did not make it to 2016, he did live until 1994, passing away at 93 years of age.

The last letter that Pauling wrote to Stone concerned a joint award from the Academy of Orthomolecular Psychiatry and the Orthomolecular Medical Society that Stone was to receive. The Linus Pauling Institute of Science and Medicine was also going to surprise him with a second award. Pauling wrote,

For many years you have been an inspiration to me, because of your devotion to vitamin C and your conviction that a high intake of vitamin C has great value in improving the health of human beings. You have rendered a great service to the people of the world through your continued study of vitamin C over a period of fifty years.

Unfortunately, Dr. Irwin Stone died on May 4, 1984, at the age of 77, while in Los Angeles to receive the award. He died by choking on regurgitated food, the result of a constricted esophagus that had plagued him ever since his car accident many years prior.

Irwin Stone received two honorary doctorates, many additional awards, and 26 patents. He also published over 120 scientific papers throughout his life (at least 50 were about vitamin C) and wrote one book, The Healing Factor, published in 1972. He was father to one son, Steven, and was married to his wife Barbara for over 50 years.

In December 1986, two years after his death, Barbara Stone sent Pauling a card congratulating him on the publication of his latest book, How to Live Longer and Feel Better. She wrote “Irwin would have enjoyed reading it and noting the many references to him and other colleagues.” Pauling hadn’t exaggerated in his 1981 letter: Irwin Stone really did change his life and made a profound impact on the scientific legacy that Pauling leaves behind today.

Irwin Stone: An Influential Man

Irwin Stone. (Image by Oscar Falconi)

Irwin Stone. (Image by Oscar Falconi)

[Part 1 of 2]

Dr. Irwin Stone was a biochemist and chemical engineer who maintained a particular interest in and enthusiasm for vitamin C. Stone was the person who first raised Linus Pauling’s interest in vitamin C, leading to Pauling’s extensive program of research on vitamin C and its uses for the prevention and treatment of disease. Pauling’s contributions to the field are one of the big reasons why many people believe in taking vitamin C for the prevention and treatment of colds today.  But for Pauling, it all started with Irwin Stone.


Stone was born in 1907 and grew up in New York City. He attended the College of the City of New York and then worked at the Pease Laboratories, a well-known biological and chemical consulting lab, from 1924 to 1934. Stone started out as a bacteriologist, but was promoted to Assistant to the Chief Chemist and then to Chief Chemist.

In 1934 the Wallerstein Company, a large manufacturer of industrial enzymes, recruited Stone to set up and direct an enzyme and fermentation research laboratory. Ascorbic acid, or vitamin C, had just been identified and synthesized by a Hungarian research team led by Albert Szent-Györgyi, who later won the 1937 Nobel Prize in Medicine for his work. Stone pioneered processes for implementing the antioxidant properties of ascorbic acid in industrial settings. One specific application that Stone developed was the use of ascorbic acid as a preservative for food – an innovation that landed him three patents.

Stone’s interest in vitamin C lasted throughout his life. He began to study scurvy intensely and by the late 1950s he had formulated a hypothesis that scurvy was not merely a dietary issue, but a flaw in human genetics. (He called it “a universal, potentially-fatal human birth defect for the liver enzyme GLO.”) Stone considered the amount of vitamin C that nutritionists recommended in a healthy diet – the Recommended Daily Allowance (RDA) – to be far from sufficient. In 1968 that recommendation was 55 mg for women and 60 mg for men. The current standard is slightly increased at 75 mg for women and 90 mg for men, with higher recommendations for pregnant and lactating women. But none of these figures are anywhere near Stone’s recommendations.

Stone believed that humans suffer from “hypoascorbemia,” a severe deficiency of vitamin C, caused by our inability to synthesize the substance the way that virtually all other mammals do. Most other mammals synthesize vitamin C in large quantities relative to body weight; proportionately, humans theoretically should be taking between 10-20 grams daily. Stone suggested that about 25 million years ago the primate ancestors of human beings lived in an environment in which they were able to consume relatively massive amounts of ascorbic acid, compared with what we get from our diets today. These material circumstances created an environment in which a genetic mutation occurred that allowed these human ancestors to stop synthesizing the substance. In present day, Stone noted, these amounts of ascorbic acid are not readily available in our diets, so humans may only be getting 1-2% of what they need.

This hypothesis initially led Stone to propose a vitamin C intake of 3 grams for optimal health, 50 times the RDA, and as he further researched ascorbic acid, he recommended increasingly higher doses. He was convinced that taking less than the amount that he recommended would cause “chronic subclinical scurvy,” a state of lowered immunity that increased susceptibility to a variety of illnesses. He felt that large doses of ascorbic acid should be used to prevent and treat infectious and cardiovascular diseases, collagen breakdown, cancer, SIDS, birth defects, AIDS, and health problems normally associated with aging.

Practicing what he preached, Stone and his wife began taking megadoses of vitamin C and they found that it greatly improved their overall health. When the couple both incurred injuries from a serious car accident, they treated themselves in part with large doses of vitamin C and reported a swift recovery. Stone attributed their rapid healing to the large doses of vitamin C.


Letter from Irwin Stone to Linus Pauling, April 4, 1966.  This is the communication that spurred Pauling's interest in vitamin C.

Letter from Irwin Stone to Linus Pauling, April 4, 1966. This is the communication that spurred Pauling’s interest in vitamin C.

In March 1966, Linus Pauling gave a speech on the occasion of his receiving the Carl Neuberg Medal for his work in integrating new medical and biological knowledge. In the speech, Pauling – who was 65 years old at the time – mentioned that he hoped to live for another fifteen years so that he might see several advances of science in medicine that he anticipated to be emerging during that time period.

Irwin Stone was in the audience at this lecture and, on April 4, 1966, he wrote Pauling a fateful letter in which he noted

You expressed the desire, during the talk, that you would like to survive for the next 15 or so years….I am taking the liberty of sending you my High Level Ascorbic Acid Regimen, because I would like to see you remain in good health for the next 50 years.

Pauling was initially skeptical of Stone’s advice, but he had recently learned about other uses of megavitamin therapy and their successes, so he decided to give the regimen a try. It was at that point that Linus and Ava Helen Pauling began taking 3 grams of vitamin C a day.

In July Pauling wrote back to Stone: “I have enjoyed reading your paper and manuscript about hypoascorbemia. I have decided to try your high level ascorbic acid regimen, and to see if it helps me to keep from catching colds.”

Pauling, as it turned out, was impressed by the results. For most of his adult life, he had suffered from severe colds several times a year and had taken a daily dose of penicillin off and on from 1948 to the early 1960s. Pauling thought that the penicillin doses were his primary defense against colds but, in all likelihood, he was probably just killing off his good bacteria and making himself more susceptible to colds through his overuse of antibiotics. Once the Paulings started taking vitamin C, they reporting a noticeable uptick in their physical and emotional energy, and seemed to suffer from fewer colds.

Two years after their initial communications, Stone noticed that Pauling had cited him in a recently published journal article. Stone described his difficulties in getting his research published and the backlash that he was experiencing from physicians. He also asked about Pauling’s health.

The last time I wrote you in 1966, you mentioned that you were going to try my high level ascorbic acid regimen to see if it would help prevent your catching colds. How did it work? At the time you also had a broken leg. I know from personal experience [a reference to his car accident] that it is excellent in bone healing.

Pauling replied

I can report that both my wife and I have been less troubled by colds during the last two years, during which we have been taking 3 to 5 grams of ascorbic a day, than we had been before beginning your regimen.

He also asked about Stone’s research on ascorbic acid and leukemia.

During the late 1960s, Pauling did not make a point of promoting vitamin C megadoses, though he did support the use of megavitamin therapy for the treatment of schizophrenia. But by 1969, he was finally fully convinced of Irwin Stone’s arguments as well as his own personal successes with vitamin C, and he began to promote vitamin C publicly.

Akira Murata

Akira Murata, 1975.

A year before being introduced to Fukumi Morishige‘s work, Linus Pauling was paying close attention to research being conducted by another Japanese colleague, Dr. Akira Murata, who was studying the inactivation of viruses by vitamin C.  Over the coming years, Morishige and Murata often worked together on research related to vitamin C.  And as with Morishige, Murata became a close colleague of Pauling’s, hosting him on numerous visits to Japan and, on at least a few occasions, traveling across the Pacific to visit Pauling in California.

Murata was born in Shimonoseki, Japan in 1935, and later attended Kyushu University, receiving his Ph.D. in microbiology in 1963.  In 1966 he accepted the position of Associate Professor at Saga University, where he has remained for the bulk of his career.

From early on, Murata was interested in vitamin C and, in particular, the impact that it could make on viruses.  In 1975 Murata summarized much of his early work in a paper written for the Intersectional Congress of the International Association of Microbiological Societies titled, “Virucidal Activity of Vitamin C: Vitamin C for Prevention and Treatment of Viral Diseases.” In it, he outlined a series of clinical trials that he had conducted with Morishige, which focused on the impact of vitamin C on viruses using phages for model systems and their host bacteria. A year later, in 1976, Murata went to the United States to study vitamin C and the immune system at the Linus Pauling Institute of Science and Medicine.

Murata and Pauling in Pauling's office, 1976.

A parallel track of research conducted by Murata and Morishige in the 1970s focused on the impact of vitamin C on hepatitis.  The duo authored an important paper titled “Vitamin C for Prophylaxis of Viral Hepatitis B in Transfused Patients,” (J. Int. Acad. Prev. Med. 1978;5(1):54–58) in which they discussed their hepatitis work.  In it, Murata and Morishige reported on a series of tests in which patients who had received blood transfusions were also given specific dosages of vitamin C.  From there, observations were made with respect to hepatitis contraction among the transfusion patients.

The researchers found that, between 1967 and 1976, no hepatitis B cases were recorded for those who received large doses of vitamin C following a blood transfusion. The paper concluded that vitamin C, in large amounts, has a “significant prophylactic effect against post-transfusion hepatitis, especially type B.”  Prior to its publication, Pauling annotated and edited Murata and Morishige’s text, adding his suggestions for how the manuscript could be improved.

In 1976, the year of his residency at the Pauling Institute, Murata also published observations made by Morishige on the effect of increased doses of ascorbic acid with respect to various viral and bacterial diseases. In their study, the duo found that ascorbic acid showed a therapeutic effect on infectious hepatitis, measles, mumps, viral orchitis, viral pneumonia and certain types of meningitis.

Murata continued this line of research through the 1980s, continually seeking out new ways to test the effects of vitamin C on human health. Like Pauling and Morishige, Murata was also highly interested in vitamin C and its possible therapeutic use with cancer. Several papers arose from this program of work, including one titled “Prolongation of Survival Times of Terminal Cancer Patients by Administration of Large Doses of Ascorbate,” (Int. J. Vitam. Nutr. Res. Suppl. 1982;23:103-113) and another listing viruses reported to be inactivated by vitamin C. Together, Pauling and Murata also served as chairmen and panel members for at least one workshop on vitamin C, immunology and cancer.

Akira Murata, Ava Helen Pauling and Linus Pauling. In Japan, 1980.

By the late 1980s, Akira Murata had contributed upwards of twenty-five publications on vitamin C and its effects upon various diseases, and Pauling continued to visit him and keep in contact. Murata typically hosted at least a portion of Pauling’s many visits to Japan, often acting in the duel capacity of scientific colleague and friend. Murata also translated a few of Pauling’s books into Japanese. Among these was Vitamin C, the Common Cold, and the Flu, the preface of which contains Pauling’s note of thanks to Murata and the observation that “it is important that everyone know about the great value that vitamin C has in improving health and in protecting against disease.” Murata also translated Pauling’s best-seller, How to Live Longer and Feel Better.

As with a few other contacts in Japan – especially Morishige – Pauling remained in close correspondence with Murata over the duration of their acquaintance, frequently discussing papers on vitamin C and exchanging ideas on new studies. The two remained friends and collaborators throughout the last two decades of Pauling’s life, both benefiting greatly from their cross-cultural exchange.

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.

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.