Vitamin C for COVID Pneumonia and More

[Part 2 of 2]

The second half of the Linus Pauling Institute’s annual Pauling Day event was devoted to a question-and-answer session with the day’s panel speakers: Anitra Carr, Alpha “Berry” Fowler, Jeanne Drisko and Maret Traber. Event moderator Alexander Michels, a researcher at LPI, fielded questions submitted by the large audience watching live on Zoom and YouTube. The conversation was dominated by intriguing work being done on vitamin C and COVID-19, though several other topics were discussed as well. Here is a synopsis of the Q&A.

How much vitamin C should we be taking?

Carr answered this question first and noted that, while a lot depends on one’s condition, studies have generally found that healthy people need about 200 mg per day. Carr added that obtaining this amount through supplements is fine, since the body will excrete any excess vitamin C that is not used, but that it is also possible to ingest this amount through fruits and vegetables alone. As mentioned by Traber in her presentation, a diet of 5-9 servings per day of fruits and vegetables will usually provide enough vitamin C. Carr added the caveat that this is only the case when at least two of those servings come from fruits or vegetables with high vitamin C concentrations; foods like kiwi fruit or oranges. Further, cooking foods decreases the bioavailability of vitamin C and should be considered when calculating one’s daily vitamin C intake.

While most panelists generally agreed with Carr, they did have some additional thoughts. Michels, the event moderator, noted that LPI recommends at least 400 mg per day, simply because most people do not know if they are in sub-optimal health or suffering from Metabolic Syndrome. Given that the 200 mg value is put forth for those who are already at optimum health, in LPI’s view it is best practice to err on the side of extra vitamin C, especially since there are virtually no side effects connected with taking a higher than necessary dose. Drisko echoed Michels’ comment and added that, because of the inherent difficulties in testing vitamin C blood plasma levels, developing an accurate assessment of need is often a challenge. In keeping once again with the idea that it is better to be safe than sorry, Drisko recommends that people go as high as they can tolerate when supplementing vitamin C. This method, which Drisko personally uses, means that intake might fluctuate from day to day, but may also yield better long-term results. Fowler agreed that supplementing is a good idea and added that he personally takes 500 mg twice per day of a buffered vitamin C, which helps to minimize some of the gastral symptoms that can arise when using higher levels of the vitamin.

Is there a difference between various forms of vitamin C?

Drisko and Carr both answered this question, and both made clear that there is no difference in terms of bioavailability from one form to another. Drisko did note that lipid-encapsulated vitamin C helps to reduce gastrointestinal symptoms and recommends its use. That said, she also cautioned that lipid-encapsulated vitamin C cannot be used in intravenous treatment.

Tell us more about the use of vitamin C in treating COVID-19.

This next question was directed initially to Fowler, who is currently running a COVID-19 and vitamin C study. Fowler explained that COVID pneumonia, which is caused by a virus, creates an infection of the airways that presents in a manner similar to sepsis. Previous research has also found that viral- and bacterial-derived sepsis present in basically the same way, and that both respond well to vitamin C infusions. Based on this, Fowler felt that there could be promise in using intravenous vitamin C to treat patients suffering from COVID pneumonia.

In Fowler’s earlier research, he found that vitamin C acts as an anti-inflammatory agent. It does so by reducing the explosion of DNA that may have escaped during illness, and that often serves as a hallmark characteristic of inflammation. Fowler has also found that vitamin C reduces tissue damage. This is important because, with COVID pneumonia in particular, the virus works to destroy lung tissue.

For his current study, patients need to be positive for COVID-19, have COVID pneumonia, and be on a ventilator. In addition to the usual standards of care for COVID pneumonia, test group patients are being given an intravenous infusion of vitamin C, with dosages based on the VCU protocol. Because the study is double blind, Fowler does not know who is in the test group, but he has already noticed a stark divide in patients’ prognosis following their treatment, with some recovering rapidly and others declining. These early observations are tantalizing and may be indicative of vitamin C making a positive impact on patients suffering from COVID-19.

Drisko also spoke about her experiences related to vitamin C treatment of COVID-19. Near the beginning of the pandemic, Drisko travelled with a team of experts to Wuhan, China, the site of the index case of the virus. In Wuhan, the team treated several nearly comatose patients with vitamin C at an infusion rate of 25-50 grams per hour; rates that are similar to the VCU protocol. These patients, who were believed to be near death, wound up recovering. More detailed information on these findings is scheduled for publication.

Michels then asked the other panelists about their impressions of vitamin C and COVID-19. In response, Carr spoke of misleading studies that have prompted a false belief that vitamin C is not effective in combatting the virus. In one example, patients were given 8 grams of vitamin C orally. As Carr explained in her prepared remarks, the bioavailability of oral vitamin C is limited by the carrying capacity of transport molecules that are found in the stomach, and is thus far less effective than is intravenous vitamin C. Regardless of this limiting factor, the study did find that symptoms shortened by about 1.2 days, but that finding was not statistically significant and the study was stopped prematurely. Carr is confident that if the trial had been designed to test IVC, it would have yielded better results. Instead, the study helped to perpetuate a pessimistic narrative surrounding vitamin C’s efficacy. As Michels added, “statistically underpowered studies are misleading people and are sadly a common thing with vitamin C.”

Next, Fowler reflected on his connection with a controversial study, the VICTUS trial, which reported a negative relationship between vitamin C and COVID-19. In this instance, doctors gave patients 1.5 g of IVC four times a day, a quantity much lower than that called for by the VCU protocol. In addition to the vitamin C, patients were given 2,000 mg per day of thiamin and 50 mg of hydrocortisone four times a day. The study did not find any significant reduction in symptoms, nor a reduction in mortality. While an author on the study, Fowler emphasized that he did not participate in its design but merely helped to administer its procedures, and he pointed out several areas for criticism. In addition to the relatively low levels of vitamin C administered, the study was privately funded, and instead of the 2,000 people the study called for, just 500 people were enrolled. While critics have cited the low number of enrollees as a primary reason for such poor results, Fowler believes it was really the low levels of vitamin C. For Fowler, 50 g really is the target range for IVC, which is what is in the VCU protocol. Michels, who agreed with Fowler, commented that with vitamin C a big lesson is that “dose matters.”

Drisko then weighed in on the issue of mis-dosing. As a long-time vitamin C researcher, Drisko is confident that there is very little risk in giving a person too much vitamin C, adding that she is soon to publish a pharmacokinetic study concluding that, when cancer patients are given vitamin C up to their tolerated dose, there is no sign of organ damage. Her study also helps to combat a pervasive myth that high doses of vitamin C lead to increased bleeding or kidney damage. While the study did find increases in patients’ calcium levels, nothing about it was alarming. (Even though vitamin C has a high osmolality, the high levels of vitamin C did not destabilize calcium levels.)

Talk about the link between vitamin C and kidney stones.

In rare instances, when people are put on IVC they can develop oxalate kidney stones. To minimize these risks, Drisko recommends that all IVC patients get their urine tested to check for signs of oxalate production, an indicator of the development of these kinds of kidney stones. But, as Drisko explained, not all kidney stones are oxalate, so having a history of kidney stones is not necessarily a contraindication for IVC. More important is the need for any practitioner delivering IVC to check their patient for an inherited G6PD enzyme deficiency, because if a person has this condition and is given IVC they can develop hemolysis and risk possible death.

Drisko and Carr also commented on the risk for kidney stones posed by oral vitamin C dosing. Both agreed that this is not something that people without a history of kidney stones need to worry about, since supplementary vitamin C doses are generally equivalent to those found in a typical diet. Carr added that many studies that have shown a connection between the development of kidney stones and vitamin C do not prove cause and effect, but rather suggest a connection. There are many factors that can lead to kidney stones, such as dehydration and diet. For Carr, the popular belief that vitamin C causes kidney stones arises from weakly supported studies that do not actually prove a connection.


Alexander Michels ended the Q&A by asking panelists to comment on the future of vitamin C research, including the funding landscape for work of this sort. Carr replied that in her experience over the past two decades, finding money for vitamin C research has not gotten much easier, but that might be changing with a greater volume of encouraging results being published. Notably, researchers have recently found that vitamin C plays a role in epigenetic mechanisms and gene regulation. These data can, in turn, help support mechanistic rationales for funding, something that has often been missing in the vitamin C field. All of that said, Carr believes that the biggest barrier to stable funding is a shared body of knowledge. Too many physicians in particular are still unaware of the importance of vitamin C, and one of her jobs as a researcher is to educate colleagues about its importance. Traber agreed and noted that it is often hard to convince practitioners to trust the evidence that vitamins are important, though as more research is published, she too is hopeful that attitudes will shift.

Vitamin C and Health: New Frontiers

[Part 1 of 2]

On February 27, 2021, the Linus Pauling Institute (LPI) at Oregon State University hosted its annual Linus Pauling Day celebration, using the occasion to also mark twenty-five years of LPI at OSU. The eponymous celebration is traditionally held on Pauling’s birthday, who on February 28, 2021 would have been 120 years old. The event this year, held a day early, was also conducted entirely over Zoom due to the COVID-19 pandemic. Because it was held in a virtual space, the event was able to attract a large audience, with moderator Alexander Michels – a research associate at LPI – noting that over 1,200 people were in attendance.

This year’s topic, “Vitamin C and Health: New Frontiers” focused on the latest research into vitamin C and its impact on human health. Four experts – Anitra Carr Ph.D., University of Otago; Alpha “Berry” Fowler III M.D., Virginia Commonwealth University; Jeanne Drisko M.D., University of Kansas; and Maret Traber Ph.D., OSU – spoke about recent trends in basic and clinical research, covering topics including cancer, sepsis, and COVID-19. The 90-minute event began with prepared comments from the speakers followed by a question-and-answer session moderated by Michels.

Event welcome slide with Emily Ho speaking at right.

LPI director Emily Ho opened the event by providing some useful background on Pauling and his contributions to vitamin C research. As Ho explained, Pauling was “a true innovator” whose research into vitamin C was not initially embraced by the scientific community, despite clear evidence of its efficacy in helping reduce infection and prevent disease. Ho also explained how Pauling viewed vitamin C as the perfect vehicle to explore ideas on orthomolecular medicine; the notion that, through the intake of “the right molecule at the right dose,” one might prevent or cure many ailments. In this, Pauling helped to “revolutionize” the connection between vitamins and health.

Following Ho’s introduction, the day’s first speaker, Anitra Carr from the University of Otago in New Zealand, began her prepared remarks. Carr has a long history of working with vitamin C. Before beginning her current position in her university’s Nutrition in Medicine Research Group, Carr worked as a researcher at LPI. In 2001, Carr’s collaboration with former LPI Director Balz Frei on vitamin C and its connection to cardiovascular health helped bring about a change in the Recommended Dietary Allowance from 60mg to the 90mg per day for healthy adults.

In her talk, Carr presented an overview of vitamin C and its relationship to fighting disease. Carr explained that most animals synthesize their own vitamin C and therefore do not require any external sources of the vitamin. But humans, along with a few other animals, lack the enzyme needed to produce their own vitamin C. As vitamin C is required by humans to sustain life – it is essential for cellular energy production, hormone and neurotransmitter synthesis, metabolic regulation and, as recently determined, gene regulation – it must be obtained entirely through the consumption of fruits and vegetables, or from supplements.

Carr also reminded audience members of Pauling’s critical role in establishing vitamin C as a viable molecule to combat disease. In the 1970s, Pauling, along with Scottish surgeon Ewan Cameron, found that intravenous vitamin C megadosing could drastically improve the prognosis for critically ill cancer patients, if not outright cure them. But this research was overshadowed by other trials conducted by the Mayo Clinic that found no changes in survival rate between a placebo group and trial group. In reviewing this history, Carr stressed that the Mayo Clinic’s trial administered vitamin C orally, not intravenously, and this difference has since been proven to be quite significant. Recent research has found that intravenous vitamin C “bypasses the regulated intestinal uptake,” meaning that a person “can get much higher levels of vitamin C” in their system when the dosing is applied intravenously. In addition to improved absorption, the intravenous approach also allows for much higher doses to be applied: present-day IV infusion bags for cancer patients contain about 70 g of vitamin C, which is equivalent to about 1,000 oranges.

From there, Carr moved on to recent vitamin C research including her own, which explores the relationship between vitamin C and colorectal cancers. Specifically, Carr and her team have biopsied colorectal tumors and found that, at their core, they contain very low levels of vitamin C. When these same patients have been dosed with intravenous vitamin C, their tumor cores show higher levels of the vitamin. This finding connects with other work suggesting that, when cancer patients have high levels of vitamin C in their tumors, their prognosis improves. This is so because “vitamin C helps white blood cells eliminate pathogens from the body.” Likewise, people who are sick often have higher blood plasma levels of vitamin C, an indication of their need for the vitamin, since any unused vitamin C is rapidly excreted throughout the body. By extension, “critically ill patients tend to have higher requirements for vitamin C.”

The next speaker was Jeanne Drisko, who spoke further on the effects that vitamin C can have on prognosis. An emeritus professor at the University of Kansas Medical Center, Drisko’s presentation focused intently on the differences between oral and intravenous vitamin C (IVC), and how these two routes of administration make big differences in the ways that vitamin C acts on the body.

As Drisko explained, for healthy people, obtaining vitamin C orally (either through diet or supplements) is usually enough to maintain proper levels. (In Drisko’s slide above, this status is indicated in green.) However, when people become sick, oral vitamin C dosing is no longer adequate. This circumstance is what Drisko calls the “primary divide” and can be seen in her chart as a progression into the redder colors. Once an individual has crossed over the primary divide, their vitamin C needs increase by orders of magnitude, from requirements in the micromolar range to requirements in the millimolar range. A jump of this sort is akin to leaping across the Grand Canyon, and not achievable through the intake of oral vitamin C. Because of the inhibitory transport molecules in the gut, oral vitamin C cannot provide the blood with millimolar levels of vitamin C, and is therefore inadequate for people who have arrived at that level of need.

In the context of IVC however, differences emerge in the way that vitamin C acts within the body, depending on the dose. In the millimolar range of IVC, vitamin C can be considered a “prodrug.” In using this type of instance, Drisko explained that vitamin C is not the actor that is creating positive health benefits, but instead is acting upon a substance that is creating the positive effects. Specifically, vitamin C (“the prodrug”) helps promote the curative powers of hydrogen peroxide (“the drug”). Vitamin C saturation can eventually reach a point where it acts as a drug, and at those levels, one crosses into the “secondary divide” where the full benefits of vitamin C can be seen. Patients can arrive at the “secondary divide” with IVC dosing of about 10 grams or more, “even up to 100 grams.” Depending on the circumstances, one can benefit from increasing up to such large doses because, as Drisko put it, “it’s a linear response; the higher the dose of IVC the higher the production of hydrogen peroxide.”

Because different metabolic changes occur depending on levels of vitamin C saturation, Drisko noted that proper dosing is a critical component of any successful IVC protocol. Drisko likened this to a scenario where a prescriber treats a MRSA patient with vancomycin, an antibiotic known to be effective with bacterial infections. The proper dose to treat MRSA is one gram every eight hours, but in the hypothetical, this doctor gives the patient just one milligram every eight hours. A prescription of this sort would necessarily mean that the patient is underdosed and will not have adequate blood levels of the antibiotic to fight MRSA. As Drisko pointed out, this scenario doesn’t mean that the vancomycin is ineffective, it just means that the wrong dose was given. As with vitamin C, “dose is critical.”

So too is the rate at which a dose is administered. From her research, Drisko has concluded that an infusion rate of 0.5-1 gram per minute – akin to about 50 grams every 1-2 hours – is ideal. And while Drisko assured her audience that these high doses are safe, there is a caveat: those with a G6PD deficiency and/or a propensity for developing oxalate kidney stones should not undergo IVC therapy because of potentially life-threatening complications. (These risk factors will be discussed in more detail in our next post).

The next presentation was delivered by Alpha “Berry” Fowler III, who spoke about the connection between vitamin C, sepsis, and COVID-19. Fowler, a professor of Medicine at Virginia Commonwealth University, has found that when people are in sepsis, their vitamin C blood plasma levels drop to alarmingly low levels that nearly approximate those found in sufferers of scurvy. This led Fowler to conclude that illness and vitamin C are linked, and that those who are critically ill are somehow using up their vitamin C at a much more rapid rate than those who are not.

Seeking to test the theory that vitamin C plays a role in disease management, Fowler received funding from the National Institutes of Health to conduct a Phase III trial titled “Vitamin C Infusion for Treatment in Sepsis-Induced Acute Lung Injury.” Fowler specifically chose to test those with lung-related sepsis due to the prevailing connection between lung disease and low vitamin C levels.

In his study, which was deployed at seven medical centers around the U.S., 170 participants were randomized, with 83 placed on a placebo and 84 enrolled in the trial. Both groups received the same standard of care for sepsis, including the use of ventilators as needed. The only difference in care was that the trial group received an infusion of vitamin C at a rate of 50mg/kg every six hours over a 96-hour period, an approach that was subsequently named the “VCU Protocol.” The research team found that those receiving vitamin C infusions had plasma levels rise from the micromolar to the millimolar level – a 6,000-fold increase. Fowler and his team then charted incidents of organ failure and death over the next five years. During this period of time, 46% of the placebo patients died, as compared to 30% of the vitamin C patients.

Buoyed by these results, Fowler is now working on expanding the initial trial to a larger scale. He is also currently involved with a study on vitamin C treatment of COVID-19 pneumonia, with 140 patients currently enrolled and using the VCU Protocol.

The last speaker of the day was Maret Traber, a nutritionist and the Ava Helen Pauling Chair at LPI. Traber’s topic was Metabolic Syndrome (METS), a designator used for a range of people who are on the verge of developing disease, including obese or pre-diabetic individuals. In the U.S., approximately 35% of adults have METS. As Traber noted, people with METS also tend to have chronically low levels of vitamin C, though why this is the case is still an open question. The good new though, is that even if people have METS, they can get satisfactory levels of vitamin C through diet alone, and don’t need to be treated with IVC. Traber recommends 5-9 servings of fruits and vegetables per day for healthy people and people with METS alike. Eating a diet of this sort will also supply adequate levels of other vitamins including vitamin E – the primary focus of Traber’s work – which can work synergistically with vitamin C to reduce free radicals in the body. 

After the panelists gave their talks, the forum was opened up to a question-and-answer session. This portion of the event will be covered in next week’s post.

Pauling’s Study of Schizophrenia: A Program of Work

[Part 3 of 9]

I feel, accordingly, that it is the duty of every psychiatrist to add megavitamin therapy, orthomolecular methods, to his armamentarium, and to make use of these vitamins, to try them out in proper amounts, not just by doubling the recommended daily allowance, but in the proper amounts as discussed by Dr. Hoffer and others here as having been found to be effective for many patients.

-Linus Pauling, speech to the American Schizophrenia Association, July 1971

Upon learning about the potential that vitamin megadosing might have for improving the lives of people suffering from schizophrenia, Linus Pauling quickly began thinking about a new research program. This process was only accelerated by his interactions with Irwin Stone, who introduced vitamin C as a potential tool for attacking mental disease, among other health maladies. One piece that Pauling still needed however, was a more complete understanding of how best to run the types of experimental trials that he had in mind. To bridge this gap, Pauling once again turned to the literature, reading everything that he could find that was even remotely related to orthomolecular protocols.

One interesting resource that Pauling consulted amidst his information gathering process was the Veteran’s Administration. Specifically, in June 1967 Pauling asked the VA’s chief of psychobiology research, Arthur Cherkin, to provide a digest of all research that had been done by the federal agency on the correlation between mental disorders with nutrition, protein deficiencies, and vitamin deficiencies. Cherkin was happy to help, supplying Pauling with notes on some 500 different studies that involved these topics.

A few months later, Pauling also reached out to Humphry Osmond to ask if he knew of any “psychiatrists, especially in California, who are sympathetic to the use of nicotinic acid, nicotinamide, and ascorbic acid in the treatment of schizophrenia.” What seems to be clear in these exchanges is that even though Pauling had read reports about the design and effectiveness of other trials, he was still pondering how best to organize his own experimental approach.


By December 1967, Pauling was feeling more ready to begin his research. His careful reading of the literature had convinced him that schizophrenia could be caused by a nutritional imbalance of nutrients, and that orthomolecular therapy could be of great benefit. He also had a good idea about the analytical tool that would drive his experiments.

From the beginning, Pauling worked closely with his University of California – San Diego colleague (and former Caltech student) Art Robinson. Together they collaborated with County University Hospital in San Diego to conduct human trial nutrient tests on patients with schizophrenia. The study initially tested the trial group’s capacity to absorb vitamin C, and was later repeated to analyze absorption of vitamins B3, B6, and B12. Importantly, as he had done in the 1940s, Pauling once again relied upon urinalysis to compile his data. In the County University Hospital trials, subjects’ urine was collected and analyzed both before and after dosing with vitamin C, which was ingested in the form of orange juice.

Art Robinson, 1974.

Though the urinalysis approach had proven unsuccessful in the 1940s work, Pauling was inspired to try it again as a result of his more contemporary reading. In one particularly relevant research notebook entry, dated July 25, 1967, Pauling analyzed a 1966 paper in which author H. VanderKamp reported on his use of urine sampling to investigate ascorbic acid and thorazine treatments for schizophrenia patients. The idea was clearly enticing for Pauling, who wrote in his journal that day, “Could a urine test be useful in diagnosis?” The answer proved to be yes, and by the time Pauling was running his human subjects trials in San Diego, he had fine tuned his approach. To test the amount of vitamin C present in a urine sample, Pauling and Robinson would use gas chromatography to detect the presence and quantities of aromatic compounds that are created when vitamin C reacts with alcohols.

The initial trials showed promise, with “all patients elevat[ing] to normal levels [of vitamin C] after eight days” of treatment. This finding aligned with Pauling’s hypothesis that vitamin C levels in schizophrenics were too low, and that through supplementation they would be able to reach “normal” levels in a relatively short period of time.


Pauling and Robinson’s first data set was exciting enough that they decided to apply for funding to expand the scale of their project. In mid-1968, the duo submitted a grant proposal titled “Orthomolecular Psychiatry – Diagnosis and Therapy” to the National Institutes of Health, requesting $336,945 (roughly $2.7 million in 2020 dollars) to support work conducted from January 1, 1969 to December 31, 1973.

The proposal outlined a plan that would follow the same general procedure as before, centering around the administration of “oral doses of substances and then to analyze samples of urine” using “chemical, microbiological, spectrophotometric, and gas chromatographic methods.” The substances that Pauling and Robinson planned to test were “ascorbic acid [vitamin C], nicotinamide [B3], pantothenic acid [B5], cyanocobalamin [B12], and pyridoxine [B6].” However, unlike the previous study, this project would also make use of controls – people who did not have schizophrenia – including “nurses, physicians, students, [and] faculty members.”

In justifying the proposal, Pauling admitted to grand ambitions, stating that

We are not attempting to carry out a definitive test of a well-defined hypothesis, but rather to discover something about mental disease. I hope that it will turn out that what we are doing now is analogous to what my coworkers and I did between 1945, when I had an idea about the nature of sickle-cell anemia, and 1949, when Drs. Itano, Singer, and Wells and I published our paper, “Sickle Cell Anemia, a Molecular Disease.”


The study was funded, and also happened to coincide with a period of rapid change for Pauling, whose institutional home shifted from UCSD to Stanford to the Institute for Orthomolecular Medicine (co-founded by Pauling and Robinson) during the lifetime of the grant. Despite all these transitions, Pauling published a number of papers as a result of the grant, all of which emphasized a positive relationship between vitamin megadosing and improved health for schizophrenia patients. As its profile rose, the work also began to attract interest from additional funding sources including, as communicated in a 1978 letter from Art Robinson, “the Multiple Sclerosis Society, the Educational Foundation of America, the National Cancer Institute, and the National Institute of General Medical Sciences.”

As the program moved forward, Pauling continued to devote time and energy to perfecting experimental design and minimizing side effects for trial participants. In his correspondence with Humphry Osmond for example, regular attention is given to defining proper dosages and best practices for maximum absorption. Taking supplements with Coca-Cola was, for instance, ill-advised, and so too with caffeinated coffee. Concerns were also raised about the sugar content in fruit juices, and eventually pure glucose was used to sweeten the vitamin C trial drinks. Likewise, milk was not recommended for any person of African or Asian descent, and at least two or three grams of bran were to be given to all patients per day “to help avoid the use of laxatives” often needed by those taking high doses of antipsychotic drugs.


One major trial that involved Pauling and Robinson as collaborators was titled “Urine Biochemistry in Schizophrenia and the Effects of Vitamin Loading,” and was carried out at the Agnews state mental hospital in Santa Clara, California. Pauling and Robinson were primarily asked to take charge of analyzing urine samples collected from the 200 schizophrenic patients recruited into the study, but the importance of Pauling’s past work clearly permeated the new trial. In the study’s introduction, lead researcher Maurice Rappaport pointed out that

Pauling, on the basis of previous research, has reached the conclusion that there are differences in the metabolism of ascorbic acid, nicotinic acid and pyridoxine between those who are in good mental health and those who are in poor mental health. Specifically he reports that among the mentally ill as compared to the mentally well, ‘there is a much larger group of people with unusually high requirements for one or another of these three vitamins.’

The sum result was

a theory of mental ill health based upon the fact that a man’s normal diet does not always supply the amount of essential nutrilites necessary to establish an optimal molecular environment for his mind. Further, [Pauling] has suggested that there are biochemical variations in some men which cause their requirements for essential nutrilites to be so unusual that the failure of their diet to satisfy these requirements results in mental illness.

Clearly Pauling’s work had made a significant impact in a short period of time. But, as we shall see, signs of trouble were soon to appear.

Pauling’s Study of Schizophrenia: A New Model Vitamin

Irwin Stone. (Image by Oscar Falconi)

[Part 2 of 9]

“I have decided, on the basis of the evidence presented by Irwin Stone, that there is very strong evidence now, that most human beings are suffering from hypoascorbemia, a mild sort of deficiency of ascorbic acid in the blood; perhaps it is wrong for me to call it a mild sort. The point that I call to your attention is that I believe that for all or almost all human beings, the amount of vitamin C that is contained in the food is less that the optimum amount, and that the state of health of almost all human beings is not so good as it would be if they were to ingest a larger amount.”

-Linus Pauling, speech to the American Schizophrenia Association, July 1971.

Linus Pauling’s chance encounter with the work of Abram Hoffer and Humphry Osmond convinced him that metabolic diseases could be treated by megadosing with certain vitamins; a practice that he labeled “orthomolecular medicine.” As Pauling’s interest in the topic grew, he sought out as much of the existing scientific literature as he could find, and quickly began to see a pattern.

As early as the 1940s, there seemed to be evidence of a positive correlation between increased niacin intake and improvement of certain psychoses in patients. The literature also supported Hoffer and Osmond’s finding that vitamin megadosing was not likely to cause significant side effects. On the contrary, many of the era’s commonly prescribed anti-psychotic drugs often caused severe side effects, sometimes even at low doses. The benefit of this new alternative was made clear by Osmond in a 1970 letter to Pauling, in which he noted that

[we are] dealing with a set of highly physiologically active substances [such as niacin] which do not, however, seem to produce the sort of danger which one finds in most physiologically active substances.

Though Pauling was convinced that orthomolecular therapy was effective, his continuing review of the literature cast doubt on whether or not niacin was, in fact, the most effective vitamin to use in treating patients with psychoses, such as schizophrenia. Though niacin was clearly safe, certain investigators had reported marginal success rates with their patients. Enough data of this sort had been reported to lead Pauling away from niacin and in the direction of a new vitamin. It was here that Irwin Stone entered his life.


In March 1966, Pauling traveled to New York to accept an award from the Carl Neuberg Society for International Scientific Relations. In his speech, Pauling – then sixty-five years old – expressed hope that he might live for another twenty years, so that he might witness the scientific advances that he believed to be forthcoming. Irwin Stone, a biochemist who worked mostly in the brewing industry, was in the audience that evening, and he felt as though he could virtually guarantee another twenty years or more for Pauling.

In a letter that he wrote after the speech, Stone told Pauling about research that he had been conducting on the health effects of vitamin C, stressing that he had been megadosing with the vitamin for the past few years and was healthier than ever as a result. In relaying this, Stone acknowledged that the story seemed implausible and admitted that he had remained a bit skeptical himself until he was involved in a car accident. Buoyed by his high dose vitamin C regimen, Stone recovered from the incident far faster than he or his doctors believed possible, and from then on he had been convinced. In Stone’s view, vitamin C would easily buy Pauling another twenty years, and maybe up to fifty!

When Stone sent his letter, he could not have known that Pauling was hatching his own interest in orthomolecular medicine; Pauling’s first paper on the subject did not appear until a year later. As such, Pauling knew that Stone’s testimony was not informed or biased by previous knowledge of his work. The letter did, however, add to Pauling’s growing belief in power of high dose supplementation in the treatment of disease. Likewise, Pauling had also been given a new model that he might explore for mental illness in lieu of the niacin trials conducted by Hoffer, Osmond and others. The next step then, was to see how effective megadoses of vitamin C might be for patients suffering from schizophrenia.

Remembering Frank Press

Frank Press

Linus Pauling’s colleague and friend, Frank Press, passed away last month on January 29, 2020 in Chapel Hill, North Carolina. Press was 95 and died of complications from a fall. Perhaps most widely known for his work as President Jimmy Carter’s chief science advisor and his twelve years leading the National Academy of Sciences, Press also collaborated with Pauling on multiple fronts, and the two ultimately grew close.

Press was born on December 4, 1924 in Brooklyn, New York. After earning his bachelor’s degree at City College of New York in 1944, Press went on to Columbia University where he earned a master’s (1946) and a Ph.D. (1949) in geophysics. During that time, Press married his high school sweetheart, Billie (nee Kallick), and the couple remained together until Billie’s death of heart failure in 2009.

After a few years teaching at Columbia, Press was offered a professorship at the California Institute of Technology, where he remained until 1965. Press left Pasadena for a position as chair of earth and planetary sciences at the Massachusetts Institute of Technology, and remained at MIT until he was asked to serve as President Carter’s science advisor and director of the Office of Science and Technology Policy.

Not long after Carter was voted out of office, Press was selected to serve as president of the National Academy of Sciences, where he remained until 1993. Following this, he took up a four-year fellowship with the Carnegie Institute as the Cecil and Ida Green senior research fellow in the Department of Terrestrial Magnetism. His fellowship concluded, Press remained on the Carnegie board for another ten years.


Press’ long and fruitful career brought him into contact with Pauling on many occasions. They first met at Caltech, but did not have cause to interact very frequently, owing to their different departmental affiliations and research agendas. The two began to find a bit more common ground through their shared interest in social justice issues concerning the United States and the Soviet Union. Like Pauling, Press pushed for both nations to sign the partial test ban treaty in 1963. Later, Pauling and Press spoke out to protest the USSR’s treatment of scientist and dissident Andrei Sakharov.

Indeed, shared interest in Sakharov seems to have prompted one of their first formal interactions, a 1983 telegram from Pauling informing Press that he had offered a job to their Russian colleague. Even though the offer did not appease the Soviets enough to release Sakharov, the telegram did catch Press’ attention. Perhaps influenced by Pauling’s actions, the National Academy of Sciences, led by Press, formally renounced the Soviet government’s mistreatment of Sakharov, and refused to participate in a joint US-Soviet scientific cooperation in 1984.


An example of the holiday cards that Frank and Billie Press routinely sent to Linus Pauling

Though Press and Pauling were not successful in securing Sakharov’s release, their shared effort on this issue created space for the two to form a friendship. As president of the National Academy of Sciences, Press sent Pauling a card nearly every year of his tenure, and Pauling become close to Billie Press as well. The friendship between the three was such that Billie often included her own note in the annual holiday card, at one point thanking Pauling for his gift of Florence Meiman White’s book, Linus Pauling Scientist and Crusader. When Pauling announced that he had cancer in 1992, the news shocked the Presses, though they were heartened to learn that he had been well enough to celebrate his 91st birthday with sixteen of his closest friends and family.

Pauling was also concerned with the well-being of the Presses, and it was here that friendship and current research intersected. As his work on orthomolecular medicine moved forward, Pauling was increasingly convinced that the Federal Recommended Daily Allowance (RDA) for certain vitamins, such as vitamin C, were far too low. Pauling believed the RDA should be much higher, and that a higher intake of vitamin C could drastically reduce the chance of developing cardiovascular disease, among other maladies.

Pauling was so convinced of this idea that he took pains to let his friends know that they could easily reduce their risk of heart disease by following the simple step of increasing their vitamin C intake. With this concern in mind, Pauling wrote to Press to urge him and Billie to have blood samples drawn so that their physician might determine the levels of lipoprotein (a) in their systems. Pauling specified that if either of their results came back elevated, “I strongly recommend that you begin a prophylactic regimen, that of taking some extra vitamin C and also perhaps 2 grams per day of L-lysin,” the latter because “the L-lysine interferes with the deposition of lipoprotein in the vascular wall.”

Pauling was also quite willing to review their results. “If the level is high,” he wrote, “there are orthomolecular measures that you should take. Let me know the results of the analyses, and I shall tell you what you ought to do.” Anticipating that the Presses might be nervous about vitamin C megadosing, Pauling wrote that a recent friend of his had used orthomolecular treatments to make a remarkable recovery after being bed-ridden following a third triple by-pass surgery. He signed the letter “Love From,” Linus Pauling.

From the correspondence, it appears as though Press trusted Pauling’s guidance. Shortly after receiving Pauling’s letter, Press replied that he would get his lipoprotein levels checked, and that he and his wife “appreciate[d] [his] interest in [their] well-being.” Press concluded the letter by noting the extent to which he and his wife “have admired you over the years.”


Several months later, in June 1992, Pauling asked Press for his help with an issue of mutual concern. Pauling’s request was spurred by an article that he had recently read titled “Reducing the Risk of Chronic Disease,” a summary of the National Research Council’s landmark, three-year study, “Diet and Health.” The aim of the study was to assist the public in making sound decisions related to their diet. (For one, the notion of “food groups” emerged from this study.)

Pauling called many of the study’s conclusions into question and, not surprisingly, took particular offense to a passage that read, “If you take a dietary supplement, do not exceed the U.S. Recommended Daily Allowance.” Because the statement was coming directly from the National Academy of Sciences, Pauling thought that he might be able to enlist Press’ support in revising its language. In his letter, Pauling was clear in his intent, writing that

I believe that this is an important matter – important to the health of nearly all Americans and other people. It seems clear to me that the members of the Food and Nutrition Board are biased against the optimum use of vitamins and are unwilling to consider the evidence. It is my duty as a member of the Academy to try and rectify this situation.

Pauling’s pleas did not fall on deaf ears. Shortly after receiving his letter, Press replied that he would pass Pauling’s concerns on to the Food and Nutrition Board (FNB) for their “thoughtful consideration” at their next meeting. Pauling’s timing could not have been better, Press explained, because the FNB had recently approved a study to look into nutrition requirements for older adults. As Press noted, this was partially due to Pauling’s inquiries into the “possible roles that antioxidant nutrients may play in preventing acute infections and chronic diseases.” Pauling passed away before the FNB had issued a verdict, but he surely took some degree of comfort at having been heard by his colleague and friend, Frank Press.

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.

Pauling, Stanford and Research – Part 2

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Pauling in lecture at Stanford University, 1969. Photo by George Feigen.

[An examination of Linus Pauling’s tenure at Stanford University. This is part 5 of 7.]

Linus Pauling knew going into his appointment at Stanford University that grants and outside funding would of paramount importance to keeping his research afloat. In September 1972 – three years into his tenure – Pauling authored a memo describing his work for the chemistry department in which he explained that his Stanford salary was now coming exclusively from grants, and that he had no other assigned duties at the university besides heading research. He likewise noted that he was actively working to bringing in new sources of money as well. In particular, he had “negotiated” a sickle-cell anemia contract with NIH earlier in June, estimating that $92,000 would be necessary from the agency.

The previous year, in spring 1971, Pauling applied for a grant from the Department of Health, Education, and Welfare to build a field ionization spectrometer for use in his urine analysis diagnoses. This device had only recently become available, the result of new technological advances in instrument design. In his application, Pauling detailed the potentially profound impact that this piece of equipment would have on his work.

This device would make possible simultaneous quantitative analysis and identification of 500-1000 chemical substances in a human body fluid in a time period of a few minutes and with an expenditure of only a few dollars per sample.

Pauling requested $387,554 for the project. It appears from a later report on his activities that he received the grant.

While Pauling enjoyed a long track record of success in attracting funding for his work, it was not always enough. In August 1972, Perry West, an administrative officer at Stanford, wrote to Pauling’s colleague and lab-mate, Art Robinson, to inform him that the laboratory’s current NIH and NSF funds would only last until the end of the year, two months short of what they had been meant to cover. As it turned out, Pauling’s laboratory had been using more computer time than they had been allocated, and had “drastically overdrawn” one account which they needed reconcile for themselves. The group has also overdrafted a second computing account that West had been funding for them.


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In addition to finding money, establishing institutional support for his research was also important for Pauling as he began to push for something a bit more ambitious: the formation at Stanford of a new Department of Orthomolecular Medicine and Nutrition. In a pre-proposal written in August 1972, Pauling called for a revitalization of nutrition as an active field of research at the university. In that same memo he also defined orthomolecular medicine “as the preservation of good health and the treatment of disease by varying concentrations in the human body of substances that are normally present in the body and are required for health.”

A few months later, in January 1973, Pauling brought his proposal to William F. Miller, Stanford’s Vice President and Provost. In making his pitch, Pauling emphasized the potential for orthomolecular medicine to bring in “millions of dollars” of funding. He also described the ways in which interest in orthomolecular research had already been taking off. By way of evidence, Pauling noted several talks that he had given the previous fall, details of which had made their way into the press.

As became readily apparent in the years that followed, Pauling also saw potential for vitamin C to treat a number of maladies including cancer, skin diseases, schizophrenia, the common cold and other infections. To begin actively investigating these tantalizing possibilities, he wanted to establish research centers at both Stanford and the University of Chicago. Miller replied to Pauling that he would consider his proposal and discuss it with the Dean of the Medical School.


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The Institute of Orthomolecular Medicine, 2700 Sand Hill Rd. Menlo Park, CA.

During this time, Pauling was also being encouraged by others reaching out to him, particularly Ewan Cameron, a surgeon and medical researcher at the Vale Leven Hospital in Scotland. Cameron shared with Pauling data related to his own successful use of vitamin C in treating bladder cancer patients. Pauling wanted to follow up on Cameron’s success and, in 1972, the two attempted to publish a paper in the Proceedings of the National Academies of Science on ascorbic acid as a treatment for cancer and other diseases. Their paper was initially rejected and, after Pauling resubmitted it, it was rejected again, an action that was described as “professional censorship” in an editorial published within the Medical Tribune.

Undaunted, Pauling continued to push his interests in developing orthomolecular medicine at Stanford and, in May 1973, proposed that the university consider building a new laboratory dedicated to the topic. In addition to the direct benefit of providing support for orthomolecular research, Pauling argued that a new laboratory would remove this work from the chemistry building, allowing it to emphasize its closer sympathies with medical research. Pauling again approached William Miller, telling him that a donor had already promised to give $50,000 for construction, which was estimated to be about half of the total cost. Pauling also expected other grants to come in as well.

Ultimately, Miller did not think it wise to pursue construction of Pauling’s orthomolecular facility. In rendering this judgement, Miller explained that Pauling had only been at Stanford for a short period of time and that his position was subject to annual renewals. This being the case, Miller did not want to “institutionalize” Pauling’s work unless Pauling was able to convince others in the chemistry and medical departments of its importance.

In effect, Pauling was told that, if he wanted his space, he would have to win over his colleagues first and convince them to initiate their own research programs in orthomolecular medicine. If this were to come about and more faculty with plenty of years ahead of them were to push for the idea, then Miller would be more open to considering a new capital project. Short of this, Miller suggested that donor funds be steered toward a more general purpose facility that would be made available to all chemistry faculty members.

Miller’s decision was important as it directly led to Pauling’s departure from Stanford University. Motivated to develop a space to pursue what he believed to be an exciting line of research, Pauling began to look for a laboratory facility off campus. This search led him to a building in Menlo Park near the Stanford Linear Accelerator. Not long after, the building became home to the Institute of Orthomolecular Medicine which, in 1974, was renamed the Linus Pauling Institute of Science and Medicine.

The History of the Pauling Blog: Of White Whales and Other Challenges

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[Extracts from an interview by Tiah Edmunson-Morton with Chris Petersen, conducted on the occasion of the Pauling Blog’s tenth anniversary. This transcript has been lightly edited for clarity. Part 3 of 4.]

Tiah Edmunson-Morton: How many students have worked on the blog?

Chris Petersen: Well, thirty-three people have written for the blog and I would say that probably more than twenty-five of them have been students. It’s mostly students.

So the people that have written for it have been students and me and a sort of random collection of other people. [Pauling biographer] Tom Hager contributed a couple of things he actually had written for something else, but we re-posted them. We also had a guy named John Leavitt, who was an employee of the Linus Pauling Institute of Science and Medicine when it was in the Bay Area, who has taken an active interest in us for a long time. And he’s been our – I called him our East Coast Bureau Chief for a while because he’s based in Connecticut. He’s sent us quite a bit of stuff and we’ve published him.

Another hat that I wear within the department is Remote Reference Coordinator, and so sometimes somebody will contact us with a fairly in-depth inquiry about Pauling and it’s going to be published in a book or in a paper or whatever. And I’ll invite them to write something for the blog and tell them that it actually has a pretty good audience and it’s going to expose your project to a wider audience than maybe it would otherwise receive. And we’ve gotten guest posts based on that as well.

But those are few and far between, relatively speaking. It’s been mostly students, and a full gamut of students too – undergraduates, master’s-seeking, and Ph.D. students. We’ve had good luck with the [Oregon State University] Honors College; we’ve recruited a lot out of the Honors College here. We’ve had good luck with the History of Science program, we’ve had good luck with the English program. But not necessarily just those three – again, there’s a bit of word of mouth from time to time, and just good luck as well happens from time to time too.

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TEM: What is the most memorable thing that a student found or researched or asked you about?

CP: Yeah, that’s an easy answer for me. I don’t know what the year was, it’s been a few years ago, but there’s a controversy – a very weird scientific controversy – on something called quasicrystals. Quasicrystals, I would not pretend to be an expert on them, but I can say that they are exotic and they are related to structural chemstry and there’s a lot of math involved.

And so I knew that Pauling had done a lot of writing and speaking about quasicrystals in the ’80s, and he got into basically a dispute with another guy named Dan Shechtman about – I think Shechtman was pro-quasicrystals and Pauling was anti, I’m honestly not even sure at this point. But there was a dispute and Shechtman was right and, as it turned out, Shechtman won the Nobel Prize in 2011 for this work on quasicrystals. And this stands as a piece of evidence about Pauling’s stubbornness and about his inflexibility at times, which was very much a part of his personality, especially as he got older.

I wanted to do something with this, but I knew that I didn’t have the ability to do it and I didn’t figure many students would either. But we finally had somebody who came across my desk who I thought, “she might be able to pull this off.” And she did.

So she devoted a lot of time to this. She was married and her husband created animated gifs to use as illustrations because she felt like that was necessary to provide context for what she was writing. And she worked from home for a while because I think she was having some health issues, and she finally emailed it to me. And she emailed it as a full package and in the email she quoted Moby Dick. And part of the quote – I don’t know the whole thing – but “from hell’s heart I stabbeth thee” was part of what she said because she had slayed this white whale of this set of posts about quasicrystals.

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And it was terrific, it really was. She was an extraordinary talent. And that was, I think, pretty much the end of her time with us; I don’t know what happened to her since, I hope that she’s done well. But she was exceptional and that really stands out in memory as just being a terrific accomplishment; something that I couldn’t have done. I think that most of what we publish is good to pretty good to excellent, and most of it I could do if I had the time and wherewithal. But I don’t know if I could have done that. She did and it was great. So, “from hell’s heart I stabbeth thee.” [laughs]

TEM: I was sort of thinking that the answer to that would not be quasicrystals but that it would be something more controversial. So Pauling also had other controversial aspects of his life and his career and I’m curious about how you’ve dealt with that?

CP: Yeah. I think that the blog is mostly friendly to Pauling and I think that’s valid. We are not an exercise in hagiography though, and we have written things that are not necessarily flattering. I think the quasicrystals instance is one of them, in fact.

The topic du jour these days is whether or not Pauling was a eugenicist, and we’ve written on that. It’s tricky, for sure, but I think we’ve taken a pretty balanced approach to that. And the last bit that we did was actually a summary of a talk that was given here by somebody from our Resident Scholar Program. So that’s been another thing that we’ve done is writing profiles on the different people who have come here as Resident Scholars to do work on Pauling; there have been several of them. And this guy gave a nice talk that, I think, presented the nuance pretty well, and I wrote that post. I was there for his presentation, I re-watched it, I wrote up the notes, and I thought a lot about how to present this. And I think that stands as a nice statement on Pauling’s point of view related to eugenics, which I’m not going to get into here. But that is one instance.

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Another instance that I think is valid is his relationship with his children. We’ve done two sets of posts on his two sons that are no longer living – Crellin was the youngest one and was actually the first one to die, and then Peter was the second oldest of the kids who had a tough life on a lot of levels. And we took a deep dive on both of them and engaged with their life stories in a way that, I’m sure, nobody else has.

Pauling, I think, he was of a different generation of parent than I am. He was very focused on his career and he had a wife who saw it as her role – early on, at least – to care for the children and to create a scenario in which he could do his work most effectively.

And he did a lot of very effective work, but I think it also had an impact on his kids on some level. I think that he loved them, I think that he certainly provided for them well after they were out of the home – most of them. But that warmth was not always necessarily there and the time was not there for sure, and that’s a criticism. And I think that comes through in the writing on some level.

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So those are a couple bits. Another thing we’ve done is written extensively about lawsuits. And he was involved in a lot of lawsuits. The ones that we’ve engaged with are well in the past and they’re libel lawsuits – mostly papers or magazines calling him a communist, and him being very litigious about it. And, so there was a Supreme Court verdict that came through that basically shot his point of view down and that was the end of him being successful with these lawsuits, but he pursued them doggedly and a sort of persnickety side of his personality arises.

He could be a little cranky at times and he probably had a right to be as far as that was concerned, but in my reading of the documents and just in his interactions with people as a writer of letters, he was always very formal and he sometimes could be pretty terse and not especially warm. So we dug into the lawsuits in significant depth and I think that showed pieces of his personality as far as that’s concerned.

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We’ve done a lot of work on vitamin C, especially vitamin C and cancer, and to a lesser degree vitamin C and the common cold, and vitamin C and heart disease. And Pauling was obsessed with vitamin C – I think that’s a fair statement – and was not necessarily willing to hear contradictory points of view very much, or perhaps pursued lines of inquiry that were not super scientific but were favorable to his perspective or were overly favorable.

And so some of that has emerged in the writing. But I also think, there seems to be a trend now – a rising trend – of scientists who are starting to think that he was on to something, and that’s been fun to document as well. So the idea basically is that if you take vitamin C orally you are not able to absorb most of it, you excrete most of it in your urine. So there’s a threshold of absorption. And he knew that, I think, but tried to suggest different ways of taking it, kind of a steady dose over the course of an entire day that would increase the concentration in the blood. But some of the things that he said were going to happen concerning the promise of vitamin C to heal in various ways were lost because you just couldn’t absorb the ascorbic acid into your body.

But in more recent time, scientists seem to be coming to the understanding that if you take it intravenously it’s a different transport mechanism and you’re able to absorb a lot more and, in fact, some of what he thought was going to happen may actually be true. And this is of, like, last Fall – there was a seminar at the Linus Pauling Institute for their Diet and Optimum Health Conference that was devoted entirely to that. So I sent one of our students to cover it and it was great. It’s really fun for me to be able to follow that a little bit and to convey that a little bit, because he took a real beating for his point of view on that. And his tactics were not the best tactics, but it’s pretty interesting to me that, these many years later, he actually may have been right about some of that stuff.

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Cameron and Pauling’s Attack on Conventional Views of Cancer

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Announcement published in the LPISM Newsletter, Spring 1979.

[An examination of “Ascorbic Acid and Cancer: A Review,” published in 1979. This is part 2 of 2.]

Linus Pauling and Ewan Cameron began their paper “Ascorbic Acid and Cancer: A Review” – published with Brian Leibovitz in Cancer Research in March 1979 – by detailing the history of research on ascorbate and establishing a connection between cancer and scurvy. This line of thinking was predicated on the observation that cancer patients, like scurvy patients, were abnormally deficient in Vitamin C. The authors, in turn, traced this observation back to the importance of Vitamin C in maintaining the balance of the intercellular matrix. They likewise emphasized that cancer is a disease that originates in the body, emanating from the patient’s own cells.

The paper next identified the two main traits of cancer: abnormal cell proliferation and invasiveness. Keeping these characteristics in mind, the authors hypothesized that the release of an enzyme, hyaluronidase, contributed to occurrences of cancer. Hyaluronidase breaks down the gel-like substance that surrounds cells, they argued, and creates a pathway that allows cells of any kind to continue multiplying. In healthy individuals, this process is self-limiting. When the process goes completely unchecked however, cells can become malignant and invade the surrounding tissue. Pauling and Cameron believed this to be the likely mechanism for metastasis, the point in a cancer’s progression at which survival rates plummet.

While they knew that it was highly unlikely that a simple infusion of Vitamin C would cure a cancer patient – as it would do in the case of scurvy – Pauling and Cameron theorized that an infusion of this sort would contribute to the inhibition of hyaluronidase, thus keeping cell proliferation in check. As they repeatedly emphasized in their review, Vitamin C’s main benefit was to increase host resistance to diseases that caused unrestrained cell proliferation. What Vitamin C did not do was guarantee complete remission.

Once they had described ascorbic acid’s defensive role, the authors moved on to its limited ability to take the offensive. One function that increased Vitamin C was believed to carry out was the capacity to “encapsulate” a tumor or disseminated tumors to the point where they were no longer malignant. As Pauling pointed out to his colleagues, when his wife Ava Helen was first diagnosed with stomach cancer and surgeons went in to remove her tumor, they noted that the mass had unusual presentation for its location and appeared to be encapsulated. Ava Helen had been taking large doses of Vitamin C for several years before she was first diagnosed, and her husband attributed the nature of her tumor and the ease of its removal to her intake of Vitamin C.


Central to the review paper were the clinical results that Ewan Cameron had compiled at the Vale of Levin Hospital in Alexandria, Scotland. Cameron had begun to see positive results early on, but found that his studies were somewhat skewed because so many of his patients were terminal and ended up dying regardless of their treatment. Cameron was worried that his data did not present much of an argument in favor of Vitamin C, a situation that was further muddied by the fact that, “the terminal stages of cancer are a compound of so many human, individual, pathological and even emotional variables, as to be nearly impossible to quantify.”

In an effort to provide what the authors believed to be a more accurate picture of Vitamin C’s treatment benefits, Cameron’s later studies measured survival time in ascorbic acid patients and compared them with non-ascorbic acid patients. This comparison revealed that a patient on supplemental ascorbic acid survived, on average, four times as long as a patient with a similar prognosis who had not received ascorbic acid.

In conducting his trials, Cameron encountered the additional barrier of patients who failed to adhere to the Vitamin C regimen once they were released from the hospital. Cameron called this mode of behavior the “reverse placebo” effect, noting that some patients, when left to their own devices, would discontinue their ascorbic acid intake because it was “just Vitamin C.” Believing that it would be treated with greater respect if it sounded more like a drug, Cameron half-jokingly suggested that pharmacies rename Vitamin C as “Pauleron” to dissuade patients from underestimating its potential.


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In the final section of their review paper, Pauling and Cameron warned of unexpected and unexplained potential consequences associated with ascorbic acid therapy. In particular, some of Cameron’s patients, after showing marked improvement for several weeks or even months, succumbed to what Pauling called a “whirlwind” of cancer. Autopsies later revealed sudden massive tumor growth and dissemination.

Interestingly, most of these “whirlwind” tumors contained a large volume of necrotic cancer cells. Pauling put forth two possible explanations for this, which he included in the review. One explanation was that, though necrotic cancer cells can be less harmful than live cancer cells, the inflammation caused by their presence might cause rapid tumor growth or become toxic to the patient in such a large volume.

A second explanation, which he thought more plausible, was based on the understanding that abruptly discontinuing Vitamin C caused ascorbate levels to plummet. In this circumstance, if ascorbic acid was inhibiting tumor growth as believed, a drastic and sudden decrease in the treatment could lead to rapid, unrestrained tumor growth.

Pauling couldn’t provide solid evidence for either possibility, but he felt that both supported the review’s hypothesis. In the first instance, ascorbic acid could be killing the cancer cells. In the second, the negative consequences of withdrawing ascorbic acid inversely suggested the benefit of continued ascorbic acid use.

Pauling and Cameron concluded their review by listing areas of ascorbate research that were encouraging but had, to date, only received preliminary investigation. Specifically, the paper pointed out that no trials had been conducted to consider the effects of ascorbate in general cancer management.


The Cameron, Pauling and Leibovitz review provoked mixed reactions. Many readers, particularly aspiring physicians, were intrigued and encouraged by the results. On the other hand, quite a few others remained skeptical and focused on the aspects of treatment that Vitamin C could not promise to provide. Shortly after the review came out, Pauling received a letter from a medical student who reported that the paper had been torn out of archived copies of Cancer Research at both Cornell Medical College and the Sloan-Kettering Cancer Center. Pauling confirmed that this had happened at both locations, but was unable to persuade anyone to rectify the situation.

In the fall of 1979, a handful of months after the review was published, the Mayo Clinic released the results of its own clinical trial, which concluded that Vitamin C did not contribute to longer survival times, nor did it offer any therapeutic benefit for cancer patients. When the results were published in the New England Journal of Medicine, Cameron wrote a letter to the editor providing a rebuttal of sorts.

In Cameron’s letter, he pointed out that the Mayo Clinic hadn’t followed the same procedures as those used at the Vale of Leven. Importantly, in Cameron’s trial, only 5% of patients had received recent chemotherapy treatment. By contrast, in the Mayo Clinic trial, only 5% of patients hadn’t received recent chemotherapy. Cameron also suggested that patients, fearful that they were in the control group and not receiving supplemental ascorbate, were dosing themselves with Vitamin C, as it was easy to obtain outside of the trial setting. If this was indeed the case, the Mayo Clinic data likely supported the Cameron-Pauling hypothesis.

Despite Cameron’s centrality to the debate, the editor of the New England journal refused to print his letter, a decision that only increased the levels of skepticism surrounding Cameron and Pauling’s work.


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In publishing their review and the papers that led up to it, Pauling and Cameron sought to update the popular view of cancer as an invasion of foreign cells that needed to be entirely destroyed to produce clinical success. Once people accepted a new view of cancer, Pauling believed that attitudes toward cancer treatment would also change.

Perhaps most importantly, Pauling and Cameron wanted physicians to stop assuming that troubling side effects were a sign of a treatment’s success and instead to begin concentrating more on the overall health of patients. Though they focused primarily on Vitamin C, the duo hoped that their review would encourage researchers to gather more evidence for an orthomolecular approach to cancer, one that would emphasize vitamins and natural methods as opposed to cytotoxic chemicals.

Although Pauling and Cameron’s perspective was not widely accepted during their lifetimes, researchers today are increasingly focusing on alternatives to chemotherapy and radiation. Immunotherapy, still in its infancy during Pauling’s life, has now become a standard treatment for certain cancers. Additionally, researchers have been able to show that high-dose Vitamin C, administered intravenously at even higher levels than Pauling and Cameron had attempted, does indeed provide therapeutic benefits in some cancers.

Ascorbic Acid and Cancer: A Review

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

[Ed Note: Today’s post is the first installment of a two-part look at Linus Pauling, Ewan Cameron and Brian Leibovitz’ extensive 1979 review of the published literature pertaining to research on ascorbic acid and cancer.]

Students of Linus Pauling’s life will know full-well that Pauling expended significant energy over his latter decades advocating for the use of ascorbic acid, or Vitamin C, in the treatment of cancer. One of his lengthier research endeavors, and certainly among his most controversial, Pauling’s interest in and advocacy of ascorbic acid therapy prompted a wide array of responses from scientists, journalists, and patients, among many others.

Pauling’s views also attracted the disdain of most medical professionals. One notable exception to this theme was Ewan Cameron, a Scottish surgeon who became so invested in the work that he eventually relocated to California to join the staff of the Linus Pauling Institute of Science and Medicine.

Prior to his immigration, Cameron had shared a rich correspondence with Pauling through which the colleagues bounced ideas off one another and even co-wrote papers. Cameron, who was head of his department at the Vale of Leven Hospital in Alexandria, was permitted to run a clinical trial testing the efficacy of ascorbic acid treatments on terminal cancer patients. He then relayed his data to Pauling, who studied the Alexandria results and contributed his thoughts on the chemical mechanisms that might be underlying them.

In 1979, Pauling, Cameron and a third author published a major literature survey titled “Ascorbic Acid and Cancer: A Review.” Appearing in the March 1979 edition of Cancer Research, the paper marked a crescendo of the duo’s eight years of work in the cancer field; work which they attempted to bolster using all of the previous and ongoing studies that they could find.

The survey, which took up ten journal pages and included 358 references, was published with the hope that it might serve to counter some of the skepticism that its authors were encountering, while also inspiring new researchers to turn their own attentions toward the potential benefits of ascorbic acid. As was typical during this period of Pauling’s career, the reception that the paper received was mixed at best.


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One of the 1,000+ references gathered by Brian Leibovitz for use in “Ascorbic Acid and Cancer: A Review.”

Pauling and Cameron first began toying with the idea of a grand literature review in 1976. Having struggled mightily with both the medical community and mainstream publishers for five years, the duo had, by 1976, finally managed to get a few papers into print. Encouraged by these successes, the co-authors agreed that gathering all available research on Vitamin C and cancer, and presenting it in one paper, would make for a very useful contribution to a decidedly nascent field.

There was a secondary ambition in play as well. Though brimming with ideas, the resources available to the two scientists were scarce and, as a result, they had arrived at an impasse of sorts. Lying at the heart of the matter was the fact that basically all of the leading medical journals had refused to publish the clinical work that Cameron and Pauling had conducted, because they hadn’t been able to follow a proper double-blind study protocol. Instead, Cameron had matched his ascorbic acid patients – by age, sex, and cancer type -with previous patients who had been treated at the Vale of Levin hospital but hadn’t received ascorbic acid.

Likewise, Cameron believed so strongly in the benefits of ascorbic acid that he refused to withhold it from incoming cancer patients who might otherwise populate a control group for his study. In his correspondence with Pauling, Cameron confided that to withhold ascorbic acid treatment from sick patients would stand as a violation of the Hippocratic Oath.

(Oddly enough, Dr. Thomas Addis – the doctor whose conservative therapies saved Pauling from an almost certain death sentence when he was diagnosed with glomerulonephritis in the 1940s – argued against the use of ascorbic acid for exactly the same reason. To discontinue traditional methods of cancer treatment he believed to be effective came at the cost of his patients, and Addis refused to do it.)

Memorial Sloan-Kettering Cancer Center in New York had conducted its own trial in 1974, but Cameron and Pauling suspected that there were problems with the scientific design of that study as well. Preventing this from happening again, especially as Pauling and Cameron were gaining increased attention from the medical community, was another motivation for publishing the review. Finally, the research that they had gathered also helped the co-authors in preparing a new book, Cancer and Vitamin C, which came out in 1979, only a few months after the review was published.


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Brian Leibovitz

In putting together their article, Pauling and Cameron enlisted the additional help of Brian Leibovitz, a graduate student at Stanford who had worked at LPISM from 1975 to 1977. Leibovitz’ main task was straightforward: obtain reprints of anything related to ascorbic acid and cancer. Pauling also requested that Leibovitz look into other papers that focused on the environment shared by cells, as he and Cameron both believed that the intercellular environment held important – if, as yet, undiscovered – resources for treating cancer.

Leibovitz expressed great dedication to the multi-year project, continuing to collect references even after finishing up at LPISM and moving to Oregon. In the end, Leibovitz gathered over a thousand sources; for his work, his name appeared on the review as a third co-author.


Once it had been completed, Pauling encountered trouble finding a home for the review. Originally a friend had offered to have it published in Cancer Research, but upon seeing the manuscript, the editor complained that the paper was much too long. In response, Cameron worked on shortening the text while Pauling looked into other avenues for publication, including The Journal of Preventative Medicine and Cancer Reviews.

While Cancer Reviews was kind enough to respond that they were not interested in publishing anything on ascorbic acid, The Journal of Preventative Medicine did not reply at all. Just as the authors were about to give up, the editor of Cancer Research got back in touch, suggesting a series of changes and promising to publish the survey once it met with the requirements that he had outlined.