Vitamin C and Cancer: Raising the Stakes

1976i2

Ewan Cameron, Ava Helen and Linus Pauling. Glasgow, Scotland, October 1976.

[Part 3 of 4]

By 1970, the year that Linus Pauling published Vitamin C and the Common Cold, the federal government’s “war on cancer” was soon to arrive. The National Cancer Act, passed in 1971, increased federal funding for treatment and prevention research, embracing cytotoxic treatment solutions like chemotherapy. That same year, Pauling began to push for investigations between nutrition and cancer, especially concerning vitamin C. Since the role of vitamin C in immune defense is arguably much less significant than Pauling supposed, the idea that intake of vitamin C should prevent or treat cancer seemed ludicrous to many physicians. Incredibly, evidence is now emerging that the opposite might be true.

In hindsight, there is a tendency for critics to see Pauling simply as a politically liberal proponent of alternative medicine; one who lashed out against a consumerist medical establishment that was firmly supported by conservative citizens, among others. However, proponents of alternative health and holism in the 1960s and 1970s prescribed to a broad range of political ideologies; Pauling was just one among many people who were searching for better preventative and alternative treatments.

In 1980, when Pauling was actively campaigning for a vitamin C treatment for cancer, Americans spent 13.1 billion dollars on cancer diagnosis and treatment. Five years later, a survey of over one-thousand individuals showed that a majority believed clinics using unorthodox cancer therapies should be permitted to operate in the U.S., and just over half said they would seek alternative treatment if seriously ill.

Pauling and his ideological positions are remembered now as having been central to the vitamin C “movement.” Perhaps this is because he was renowned in many arenas and easily attracted a great deal of media attention. Or perhaps, especially knowing his penchant for protesting against nuclear weapons testing and war, this was another issue on which Pauling was the most outspoken opponent of what he saw as a wrong to be made right.


1979p.1_new

Table from “Ascorbic acid and cancer: a review”, co-authored by Pauling and Cameron, 1979.

For Pauling, the continuing suffering of cancer victims was unnecessary, since a useful treatment was already cheap and readily available. He argued that,

The involvement of ascorbic acid (vitamin C) in the natural defense mechanisms is now known to be so great that we hope that a really significant control of cancer might be achieved by the proper use of ascorbic acid.

Of the studies that Pauling found so convincing, none were as crucial as those conducted at the Vale of Leven Hospital, near Glasgow, Scotland. There, Dr. Ewan Cameron found that mega doses of vitamin C (10 grams daily or more) seemed to slow and even reverse cancerous growth in some patients. He wrote to Pauling in 1971, who eagerly responded that this “attack” on cancer was the most promising application of vitamin C that he knew of.  Pauling, who had been studying the role of dietary vitamin C in issues of orthomolecular psychiatry such as schizophrenia, now shifted his focus to cancer.

Far from being the flaky alternative health guru that many came to see him as, Pauling’s work with vitamin C— like all his research on the subject of orthomolecular medicine (a field that he spearheaded)— was consistent with a biomedical model of molecular disease. Since Pauling saw this work as fitting within the framework of molecular biology, it was frequently unclear to him why the medical community resisted what was, to him, a straightforward and significant scientific endeavor.

Further complicating matters was the fact that Stanford University, Pauling’s academic home at the time, rejected his request for additional lab space to pursue cancer research. Now the target of regular media pummelings, Pauling’s ideas were becoming a potential source of bad press for the university. Refusing to take no for an answer, Pauling and his young lab assistant, Arthur Robinson, solicited private funding to continue their work on vitamin C outside of the university setting. Raising $50,000 in donations from wealthy supporters of vitamin therapies, the duo helped to found the Institute for Orthomolecular Medicine in 1973, subsequently renamed the Linus Pauling Institute of Science and Medicine (LPISM) one year later.

From 1973 to 1976, Pauling published co-authored articles with Cameron, who continued to study the effects of vitamin C on cancer from his base in Glasgow. And in 1975, Pauling and Robinson secured additional funds to begin their own animal testing. Two years later, the collaborators began reporting their results in the Institute’s newsletter.  In 1979 Cameron and Pauling likewise published an extensive review article in Cancer Research that cited previous studies corroborating their own conclusions. The duo published their book, Cancer and Vitamin C, that same year.


Sci 11.044, 44.14

A sample of Pauling’s notes compiled in response to the Mayo Clinic trials, 1979.

Cameron and Pauling’s data seemed to show that vitamin C would be especially valuable for cancer patients. Whereas a daily intake of 10 g of vitamin C in a healthy individual would bring the vitamin C level in the blood to a saturation point that could not be exceeded by increasing or prolonging intake, cancer patients showed a different pattern. Known already to have abnormally low blood levels of vitamin C, the patients in fact achieved just over half the same level of vitamin C blood saturation found in healthy individuals subscribing to a daily intake of 10 grams. For those afflicted with cancer, it was seen as necessary to take 10 grams a day just to reach the normal level of vitamin C found in healthy individuals who did not take supplements at all.

To Pauling, this alone justified continued research on the matter. After persistently stating his case to Dr. Vincent De Vita, director of the National Cancer Institute, two rounds of trials were conducted through the Mayo Clinic to solve what the medical community perceived to be problems in Cameron’s studies. When the trials indeed failed to produce anything like Cameron’s results, funding effectively dried up for vitamin C research – a significant blow to LPISM’s functional well-being.

In response, Pauling and his supporters argued that the Mayo Clinic was missing the point. The Mayo trials had attempted to measure the effectiveness of vitamin C in a manner similar to drug treatments, because the advent of chemotherapy and antibiotics, and the biases of the pharmaceutical industry, had placed primary medical emphasis on the disease, and not on the patient. Pauling saw the results of the Mayo studies not as a definitive defeat, but as the triumph of a complex of interdependent federal and private organizations that held a vested interest in supporting the chemotherapy status quo.


Pauling had claimed that, with vitamin C, lifespan could be increased, tumors could regress, and even full recovery was possible. For many in the medical community, these were not only foolish assertions, they were dangerous as well.

Dr. Charles Moertel, chairman of the Department of Oncology at the Mayo Clinic, was particularly vocal in his rebuke, stating that

For such a message to be conveyed to desperate and dying people, with the endorsement of a Nobel laureate, the presumption must be that it is based on impeccable scientific methodology.

Moertel’s implication, of course, was that Pauling’s argument was instead based on unsound science and certainly lacked the scientific basis to challenge the use of chemotherapy.

Yet vitamin C retained a broad appeal because many saw the prevailing treatment, and its manifold side effects, as inhumane. John Cairn, head of the Mill Hill Laboratory of the British Imperial Cancer Research Fund, provided a voice to the other side the coin by calling out the survivorship data. To wit: in 1986, 200,000 patients were receiving chemotherapy and, by 1991, five year survival rates for colon cancer remained at just 53%. Cairn spoke for many in suggesting that, when it came to the prevailing course of treatment, “the benefit for most categories of patients has yet to be established.”


1981i.3

Ava Helen Pauling, June 1981.

For Pauling, the debate turned from the public to the personal when, at the height of his study of vitamin C, his wife Ava Helen was diagnosed with stomach cancer. Following Ewan Cameron’s advice, she took 10 grams of vitamin C daily, and did not receive chemotherapy.  Throughout her treatment, Linus clung to the belief that mega doses of vitamin C would work for Ava Helen, just as it had for Cameron’s success stories in Scotland.

“Daddy was convinced that he was going to save her,” remembered Linus and Ava Helen’s daughter, Linda. “And that was, I think, the only reason he was able to survive… He said to me after she died that until five days before, he thought he was going to be able to save her.”

Ava Helen Pauling passed away in December of 1981. And though he was badly shaken by his wife’s death, belief in the value of vitamin C in the fight against cancer did not fade from Pauling’s mind. Suffice it to say, the medical community remained whole-heartedly unconvinced.

Advertisements

Vitamin C and the Common Cold: The Roots of Controversy

Detail from "The Perils of Pauling", National Observer, November 27, 1971.

Detail from “The Perils of Pauling”, National Observer, November 27, 1971.

[Part 1 of 4]

Growing up in the United States, many children today are told to drink plenty of orange juice to get their vitamin C, in part to avoid getting a cold. And indeed, vitamin C is now widely accepted as an important nutrient. Its antioxidant properties are valuable to cellular health and can protect against heart disease as well as the genetic damage that can lead to cancer and other dysfunctions. It aids the body’s production of collagen and other connective tissues, and is important for optimal healing from injury. It is also implicated in optimal neurotransmission (brain function), and stimulates the production of white blood cells important for immune health. This basic component of healthy living has been repeated so many times on television shows like “Sesame Street,” or in the classroom, or at home around the dinner table, that American children grow up recognizing vitamin C’s  importance as an obvious fact of life.

Perhaps surprisingly then, there is still little consensus in the medical community as to the ability of Vitamin C to significantly reduce the incidence, duration, or severity of the common cold. For Linus Pauling in 1971, it seemed so clear that Vitamin C was critical to human health that he felt compelled to publish his best-selling book, Vitamin C and the Common Cold, feeling that to withhold such simple and valuable information for the public’s general well-being would be negligent. His work sparked a vitamin C craze in America: after the book’s publication, consumption of vitamin C increased so much that bulk prices nearly tripled. The public certainly believed Pauling. Professional physicians, on the other hand, were highly critical.


While the full benefits of vitamin C are better known now than was the case in Pauling’s day, even in the 1970s no one argued against the vitamin’s fundamental importance. The real argument that emerged was about how much Vitamin C was enough, and why.

Oranges and other fruits and vegetables were known to prevent scurvy from at least 1753, when British naval physician James Lind reported on its effectiveness in treating this disease of nutritional deficiency. Vitamin C was first isolated in the early 1930s by Albert Szent-Györgyi, William Waugh, and Charles Glen King, and produced in the lab shortly after by Norman Haworth and Edmund Hirst. Unlike most mammals, human beings do not naturally synthesize vitamin C within our own bodies. Along with Guinea pigs, other primates, and fruit bats, we need to acquire the entirety of our vitamin C through our diet. The Federal Recommended Daily Allowance (RDA) was duly set at 60 mg each day – enough to keep one from falling prey to scurvy – by the time that Pauling arrived on the scene.


Irwin Stone. (Image by Oscar Falconi)

Irwin Stone. (Image by Oscar Falconi)

To Irwin Stone, “giving someone enough vitamin C to prevent scurvy was like feeding them just enough to keep them from starving.” Stone, a biochemist, published on Vitamin C as a food preservative beginning in 1935. In the course of this research, he discerned that a 150 lb human would need to ingest 4 to 10 grams of Vitamin C a day in order to match what a healthy rat produces on its own.

Stone met Pauling in 1966, not long after Pauling had delivered an acceptance speech for the Carl Neuberg Medal, awarded for Pauling’s assessment of sickle cell anemia as a molecular disease. In the speech, Pauling expressed his hope that he might live to see the medical advances that the next 15 years might bring. Afterward, Stone recommended that with vitamin C, Pauling (who was sixty-five years old at the time) might see the advances of the next fifty.  His interest piqued, Pauling began taking 1 gram of Vitamin C per day, and by the late 1970s, this increased to 10 or more grams daily. Around the same time, the RDA was lowered to only 45 mg. In other words, Pauling was now taking over one hundred and sixty times the daily dose of Vitamin C recommended by the government.


The concern in the medical community was, and continues to be, the potential for “overnutrition”; i.e., negative physical effects associated with consuming too much of a particular vitamin or mineral. As Pauling’s ideas gained increasing cultural currency, physicians began to warn that vitamin C consumed in such large doses might cause the development of kidney stones. Pauling countered that this was only likely in a small segment of the population – those with pre-existing hyperoxaluria – and that it could be entirely avoided by ingesting sodium ascorbate pills rather than ascorbic acid or natural sources. Pauling pointed out that, in fact, there were no health problems associated with high dose vitamin C intake other than potential stomach irritation and loose bowels – symptoms now known to occur with a daily intake of approximately two grams. For Pauling, the decision to take large doses in spite of these drawbacks seemed obvious.

But for many clinicians it was not. Leading nutritionist Dr. Victor Herbert attacked Pauling’s claims as unsupported, as did FDA head Charles Edwards, who denounced Pauling as spurring a national frenzy over vitamin C with no scientific basis. This backlash begged the question, if the benefits of Vitamin C were really medically obvious, then why would physicians mislead the public?

Medical Tribune, June 6, 1973.

Medical Tribune, June 6, 1973.

Pauling’s answer, as delivered through the media, provoked even greater controversy. Physicians were misleading the public, he said, because the reality of a cheap, safe alternative to expensive pharmaceuticals would prove economically disastrous for the medical industry. In other words, the physicians, in partnership with drug companies, had an economic interest against vitamin C. “Every day,” Pauling explained, “even every hour, radio and television commercials extol various cold remedies… I am convinced by the evidence now available that ascorbic acid is to be preferred to the analgesics, antihistamines, and other dangerous drugs that are recommended for the treatment of the common cold by purveyors of cold medicines.”

Pauling’s assertion was based in part on the opinion of Albert Szent-Györgyi, who had first isolated Vitamin C, and who told Pauling in a personal letter that,

…right from the beginning I felt that the medical profession misled the public. If you don’t take ascorbic acid with your food you get scurvy, so the medical profession said that if you don’t get scurvy you are all right. I think this is a very grave error. Scurvy is not the first sign of the deficiency, but a premortal syndrome, and for full health you need much more, very much more. I am taking, myself, about 1 gram a day.

Pauling was also drawing on the opinion of others in the medical field, such as Dr. Douglas Gildersleeve, who stated in a 1967 Fact magazine article that,

having worked as a researcher in the field, it is my contention that an effective treatment for the common cold, a cure, is available, that is being ignored because of the monetary losses that would be inflicted on pharmaceutical manufacturers, professional journals, and doctors themselves.

Pauling, in other words, wasn’t alone in staking out this controversial ground.

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.

Continue reading

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.