Pauling’s Final Years

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Pauling posing at lower campus, Oregon Agricultural College, ca. 1917.

[An examination of the end of Linus Pauling’s life, part 1 of 4]

In 1917, at sixteen years of age, Linus Pauling wrote in his personal diary that he was beginning a personal history. “My children and grandchildren will without doubt hear of the events in my life with the same relish with which I read the scattered fragments written by my granddad,” he considered.

By the time of his death, some seventy-seven years later, Pauling had more than fulfilled this prophecy. After an extraordinarily full life filled with political activism, scientific research, and persistent controversy, Pauling’s achievements were remembered not only by his children, grandchildren and many friends, but also by an untold legion of people whom Pauling himself never met.

Passing away on August 19th 1994 at the age of 93, Pauling’s name joined those of his wife and other family members at the Oswego Pioneer Cemetery in Oregon. What follows is an account of the final three years of his life.


 

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Linus Pauling, 1991.

In 1991, Pauling first learned of the cancer that would ultimately take his life. Having experiencing bouts of chronic intestinal pain, Pauling underwent a series of tests at Stanford Hospital that December. The diagnosis that he received was grim: he had cancer of the prostate, and the disease had spread to his rectum.

Between 1991 and 1992, Pauling underwent a series of surgeries, including the excision of a tumor by resection, a bilateral orchiectomy, and subsequent hormone treatments using a nonsteroidal antiandrogen called flutamide. During this time, Pauling also self-treated his illness with megadoses of vitamin C, a protocol that he favored not only for its perceived orthomolecular benefits, but also as a more humane form of treatment than chemotherapy or radiation therapy.

Pauling’s interest in nutrition dated to at least the early 1940s, when he had faced another life-threatening disease, this time a kidney affliction called glomerulonephritis. Absent the aid of contemporary treatments like renal dialysis – which was first put into use in 1943 – Pauling’s survival hinged upon a rigid diet prescribed by Stanford Medical School nephrologist, Dr. Thomas Addis.  At the time a radical approach to the treatment of this disease, Addis’ prescription that Pauling minimize stress on his kidneys by limiting his protein and salt intake, while also increasing the amount of water that he drank, saved Pauling’s life and led to his making a full recovery. Though his famous fascination with vitamin C would not emerge until a couple of decades later, Pauling’s nephritis scare instilled in him a belief that dietary control and optimal nutrition might effectively combat a myriad of diseases. This scientific mantra continued to guide Pauling’s self-treatment of his cancer until nearly the end of his life.

Pauling also believed that using vitamin C as a treatment would, as opposed to chemotherapy, allow him to die with dignity. Were his condition terminal and his outlook essentially hopeless, Pauling felt very strongly that he should be permitted to pass on without “unnecessary suffering.” Pauling’s wife, Ava Helen, had died of cancer in December 1981. She too had refused chemotherapy and other conventional approaches for much of her illness, a time period during which Linus Pauling had helped his wife the only way he knew how: by administering a treatment involving megadoses of vitamin C. This attempt ultimately failed and, by his own admission, Pauling never really recovered from his wife’s passing.

Nonetheless, Pauling continued to lead research efforts to substantiate the value of vitamin C as a preventive for cancer and heart disease in his capacity as chairman of the board of the Linus Pauling Institute of Science and Medicine (LPISM). By the time of his own diagnosis in 1991 however, the Institute was in a desperate financial situation, several hundred thousand dollars in debt and lacking the funds necessary to pay its staff.


 

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In 1992, while he recovered from his surgeries and managed his illness, Pauling continued to act as chairman of the board of the LPISM. No longer able to live entirely on his own, he split his time between his son Crellin’s home in Portola Valley, California, and his beloved Deer Flat Ranch at Big Sur. When at the ranch, Pauling was cared for in an unofficial capacity by his scientific colleague, Matthias Rath. Pauling was first visited by Rath, a physician, in 1989, having met him years earlier in Germany while on a peace tour. Rath was also interested in vitamin C, and Pauling took him on as a researcher at the Institute. There, the duo collaborated on investigations concerning the influence of lipoproteins and vitamin C on cardiovascular disease.

Not long after Pauling’s cancer diagnosis, a professor at UCLA, Dr. James Enstrom, published epidemiological studies showing that 500 mg doses of vitamin C could extend life by protecting against heart disease and also various cancers. This caused a resurgence of interest in orthomolecular medicine, and it seemed that Pauling and Rath’s vision for the future of the Institute was looking brighter.

As it happened, this bit of good news proved to be too little and too late. LPISM had already begun to disintegrate financially, its staff cut by a third. The Institute’s vice president, Richard Hicks, resigned his position, and Rath, as Pauling’s protégé, was appointed in his place. Following this, the outgoing president of LPISM, Emile Zuckerlandl, was succeeded by Pauling’s eldest son, Linus Pauling Jr. Finally Pauling, his health in decline, announced his retirement as chairman of the board and was named research director, with Steve Lawson appointed as executive officer to assist in the day-to-day management of what remained of the Institute.

One day prior to his retirement as board chairman, Pauling signed a document in which he requested that Rath carry on his “life’s work.” Linus Pauling Jr. and Steve Lawson, however, had become concerned about Rath’s role at the Institute, and particularly on the issue of a patent agreement that Rath had neglected to sign. Adhering to the patent document was a requirement for every employee at the Institute, including Linus Pauling himself. When pressed on the issue, Rath opted to resign his position, and was succeeded as vice president by Stephen Maddox, a fundraiser at LPISM.

After this transition, Pauling met with Linus Jr. to discuss the Institute’s dire straits. Pauling’s youngest son, Crellin, had also became more active with the Institute as his father’s illness progressed, in part because he had been assigned the role of executor of Pauling’s will. Together, Crellin, Linus Jr., and Steve Lawson struggled to identify a path forward for LPISM. Eventually it was decided that associating the Institute with a university, and focusing its research on orthomolecular medicine as a lasting legacy to Pauling’s work, would be the most viable avenue for keeping the Institute alive. The decision to associate the organization with Oregon State University, Pauling’s undergraduate alma mater, had not been made by the time that Pauling passed away.

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Vitamin C and Cancer: Rays of Hope

 

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[Part 4 of 4]

Ridiculed by the medical profession for two decades, the tide began to shift for vitamin C and cancer starting in 1992. That year, the New York Academy of Sciences voted to discuss high-dose vitamins and nutrients at its annual meeting, devoting several sessions to the antioxidant properties of vitamin C and its potential value at higher-than-dietary amounts in preventing lung, stomach, colon, and rectal cancers.

Oddly, throughout the proceedings, one prominent name had been missing from the conversation, a point noted by a professor from Alabama who finally spoke up, saying,

For three days I have been listening to talks about the value of large intakes of vitamin C and other natural substances, and I have not heard a single mention of the name Linus Pauling. Has not the time come when we should admit that Linus Pauling was right all along?


Since 1996 the Linus Pauling Institute, relocated from California, has continued work on cancer from it’s new home at Oregon State University. Basing these contemporary orthomolecular studies on the hard sciences of cellular biology, molecular biology, and organic chemistry, the Institute continues to explore the cutting edge of health and nutrition research.

Working under Dr. Balz Frei, the current director of the Institute, as well as former LPI principal investigator Dr. Roderick Dashwood (now director of the Center for Epigenetics and Disease Prevention at Texas A&M University), OSU student Matt Kaiser has spent time analyzing the benefits of vitamin C treatment for colorectal cancer, which remains the third leading cause of cancer related deaths in the United States. The Pauling Blog has interviewed Kaiser in the past, and we met with him again recently to gain a better sense of trends in the community of researchers interested in vitamin C and cancer.


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One primary question that begs further exploration is, why didn’t earlier studies find evidence of the value of vitamin C?

As it turns out, the problem appears to have been primarily located in the way that vitamin C was being administered. The 1979 Mayo studies to which Pauling so strongly objected had assumed that, since vitamin C was filtered out of the body after a certain point of blood saturation, higher doses need not be examined. This assumption – that excess vitamin C could not be absorbed and was simply excreted in the urine – was one of the most basic issues of contention that Pauling was never able to get past with the medical community. However, it now appears that the assumption applies only if vitamin C is taken as an oral supplement, a breakthrough that was first identified by Mark Levine, a Senior Investigator at the National Institutes of Health.

Matt Kaiser explains

Mark Levine realized in the 1990s that the way drugs are distributed and function in the body [pharmacokinetics] can drastically change the amount of vitamin C entering blood plasma. Eating vitamin C you can only get about 250 micromolar [a measure of vitamin C, or ascorbate— to use its chemical name— that can be concentrated in the blood stream]. With intravenous injection, the levels are much larger: 200 times. One millimole is a thousand micromoles, so 30 millimolar [of ascorbate in blood plasma] is a huge difference!

At these high pharmacological— or even super physiological— doses, Levine found that cancer cell populations dropped significantly. To understand why, it is important to know a bit about how cancer works.

Human DNA can wrap up tight (heterochromatin) or unwind into a loose, more open configuration (euchromatin). When it is wrapped up tight, the genetic information on the DNA cannot be expressed. This is because transcription, which is the process by which a cell reads and expresses the genetic code, requires access to DNA.

There are very specific times when DNA should be wrapped tight to maintain optimum health, and other times when one’s body needs to be able to use the instructions for cellular function that are contained in DNA. When DNA needs to be unwound, molecules called histone acetyltransferases (HATs) help to unwind it. When it needs to be wound up tight, the process is aided by histone deacetylases (HDACs).

HDAC overexpression is a hallmark of cancer cells, and hyperactive HDAC cells lead to messy, knotted DNA winding. This biological circumstance hinders the cell from reading important instructions found in DNA, which in turn prevents the production of important tumor suppressor proteins. At the same time, it leaves certain sections of the genetic code open that should not be expressed.

“Basically,” says Kaiser, “You remove the break from the car, and then you also step on the gas. And that’s cancer.”


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Matthew Kaiser.

The prevailing theory of how vitamin C acts on tumors is that it functions as a “prodrug,” meaning that it stimulates biochemical processes that allow something else to kill the cancer cell, rather than acting on it directly. In this case, the active agent is hydrogen peroxide, which is produced in saturated tissues by excess vitamin C. “Vitamin C acts as the Trojan horse that allows hydrogen peroxide to enter the tumor site,” Kaiser explains. “You can’t inject it straight in; your body will react too strongly. Hydrogen peroxide is a reactive oxygen species…it tears cells apart.”

However, since working on the project, Kaiser has found that this consensus on how vitamin C fights cancer isn’t necessarily the whole story. Pharmacological levels of ascorbate appear to selectively reduce the presence of proteins that regulate reactive oxygen species, like hydrogen peroxide, in cancerous cells. Some of these same proteins also happen to promote cell growth, which is not something that one would wish for cancer cells to do. In addition to producing hydrogen peroxide, ascorbate actually inhibits the runaway HDAC production that makes cancer cells so dangerous.

“What makes it really hard, really complicated,” Kaiser laments, “is that this might not work the same way for different types of cancer cells in different locations. There’s still so much to understand about how vitamin C is having this protective effect…That’s what’s lacking and that’s why we need studies like this.”


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And indeed, more studies are coming. In keeping with it’s mission to extend and promote what it calls “healthspan,” LPI hosts a bi-annual Diet and Optimum Health Conference, bringing together experts from around the world to talk about topics in orthomolecular medicine, among other fields. This year the conference, which was held at OSU in September, featured several speakers discussing vitamin C and cancer. One of them was Dr. Mark Levine, the NIH scientist who first showed the value of intravenous ascorbate.

Margreet Vissers and Anita Carr, of the University of Otago in New Zealand, also described their own advances on the subject. Vissers found in her studies that levels of 50 micromolar ascorbate in blood plasma (average dietary levels are between 40 and 80) had little to no protective effect against cancer. Doubling the amount to 100 micromolar, however, boosted a patient to the lowest level of the protective range. It would seem, then, that Pauling was right to suggest that mega doses might be important for optimum health.

Vissers also explained that, in animal models, ascorbate injected intravenously will peak after about twenty hours in both healthy tissue and in tumors. However, unlike the healthy tissue, tumor tissues hold onto the vitamin C and do not return to a natural baseline. This detail is important because it allows high doses of ascorbate to build up in tumor tissue, and these doses disproportionately kill cancer cells instead of healthy tissues for reasons that are still not fully understood.

Conversely, the dangers of using vitamin C, even in high intravenous doses, appear to be small. While some people harbor an enzymatic deficiency that can cause a severe negative reaction, most individuals simply cannot overdose on vitamin C. Even in the blood plasma, vitamin C usually reaches a saturation point and is filtered from the body.

At the LPI conference, Dr. Carr pointed out that this form of treatment also dramatically improves the quality of life of cancer patients as compared to chemotherapy. For one, vitamin C treatments involve significantly less pain, mental and physical fatigue, nausea and insomnia. As of March 2015, three clinical trials involving pharmacological levels of ascorbate have been conducted, all of them showing that it is well tolerated by patients and reduces chemotherapy-related toxicity.

Additionally, vitamin C at high doses is known to aid cognitive function, and these positive benefits work together to aid in social satisfaction for the patient. As Pauling pointed out in the 1970s, it is not only the disease that the doctor should be concerned about treating, but the patient as well.


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Pauling in 1989 – an extraordinary life. Photo by Paolo M. Sutter.

So is Linus Pauling vindicated when it comes to vitamin C and cancer? The answer is complicated.

On the one hand, it would appear that vitamin C can serve as an important preventative and treatment for cancer. However, the method that Pauling advocated— taking large supplemental doses orally— is pretty clearly not an effective form of application. Rather, contemporary research indicates that the levels of ascorbate that are required to slow or stop tumor growth are far greater than that which can be achieved naturally by ingesting vitamin C; they can be accomplished only by intravenous injections of ascorbate. Furthermore, it is likely that this form of treatment will not replace, but instead will augment, existing protocols including chemotherapy.

But the broader trend is optimistic and, one might argue, validating. And with the Linus Pauling Institute and many others around the world continuing to investigate the potential for vitamin C and other nutrients to help people live longer and feel better, exciting new studies on optimum diet and effective treatments for diseases like cancer would appear to be on the near horizon.

Vitamin C and Cancer: Raising the Stakes

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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.


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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.


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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.”


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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.

Vitamin C and the Common Cold: Pauling vs. the Physicians

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Diary entry by Linus Pauling, 1980. The text reads: “L[inus] P[auling] / Found enzymes enthralling / He was filled with glee / By Vitamin C”

[Part 2 of 4]

As a double Nobel laureate, Linus Pauling’s recommendation that everyone ingest 1 to 4 grams of vitamin C daily developed into a media frenzy. And with time, the debate took on a distinctly political flavor, with the battle over vitamin C argued on talk shows and in press releases, rather than vindicated in the lab.

Pauling’s accusations that the medical establishment was ignoring the potentially profound benefits of vitamin C in part because of a mutually beneficial relationship with Big Pharma did not, as one might expect, go over well with many medical professionals. Indeed, his work with vitamin C was written off by many as a passing craze, and Pauling was increasingly referred to as a “kook” and a medical “quack.”


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Notes by Linus Pauling regarding vitamin C and the common cold, 1974.

As Pauling and the physicians went back and forth, the two sides sometimes found themselves citing the same data and producing opposite conclusions. Often Pauling argued that the studies under consideration – discarded by dissenting physicians for apparently showing negligible effects – actually suggested a real value to the use of vitamin C that would be amplified if only larger doses were used.

One study in particular, authored in 1942 by A.J. Glazebrook and Scott Thomson, found vitamin C to only slightly decrease the occurrence of colds and their symptoms in a sample of college students. For proponents, the work was heralded nonetheless as significant evidence in vitamin C’s favor. The problem, Pauling believed, was that physicians expected vitamin C to act like a drug, with a concomitant “tendency…to use relatively small amounts and look for big effects.” But vitamin C wasn’t a drug, it was a nutrient, and Pauling thought its effects would not be easily observed in a typical physician’s research paradigm.

In an effort to put the issue to rest, a University of Maryland study in which eleven prisoners were given 3 grams of vitamin C a day for two weeks found that, when inoculated with cold viruses, each subject became ill. While many considered this proof that Pauling was wrong, he dismissed this study as well. For one, it lacked a placebo control group and did not take the severity of symptoms into account. Pauling likewise suspected that the prisoners were infected with a cold virus potent enough to have overwhelmed any protective effect from vitamin C.

On and on the debate raged and, by the time of Pauling’s death in 1994, little consensus had been reached: Pauling stood firm in his beliefs and the physicians hadn’t from their position.


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Harri Hemilä

Today, while Pauling’s faith in and advocacy of vitamin C has endured in the public consciousness, it has not translated into concrete medical practice. Presently, the United States Food and Nutrition Board has set the Recommended Daily Allowance for Vitamin C at 120 mg at the highest (for pregnant women), nearly three times greater than the RDA in the 1970s, but still about 100 times lower than the levels that Pauling believed to be optimal.

So what does the research really show? Is there, in fact, zero evidence that Vitamin C prevents or cures colds, as the Food and Drug Administration once claimed?

Perhaps the best summation of the current state of affairs has been compiled by Dr. Harri Hemilä, a researcher in public health at the University of Helsinki. Hemilä, whose 2005 comprehensive study on the subject is cited by the National Institutes of Health, makes a number of intriguing points.

For one, Hemilä points out that, while the broad body of research seems to indicate that vitamin C supplementation does not decrease cold incidence in most individuals, it does significantly decrease incidence in marathon runners, skiers, and soldiers – all groups subject to consistent exposure to cold weather or physical stress – by as much as 50%. Daily supplements also appear to decrease the symptoms and duration of colds by a modest degree – observations of 14% in children and 8% in adults.

It is important to note that studies of this sort have used what Pauling would have considered to be minimum dosages for optimal health – 1 to 2 grams daily. To date, few investigations have looked into doses higher than 2 grams, presumably because it is known that, for oral doses of more than 1 gram, absorption rates fall below fifty percent. The operating idea then, is that for supplementation above 2 grams, most of the extra vitamin C is unused and excreted in one’s urine.

Yet there does exist some evidence of a more significant impact at higher dosage levels. Hemilä’s survey of the research concludes that, in some studies, doses larger than 2 grams do appear to provide some measure of therapy, if taken at the onset of cold symptoms.

Digging more deeply into the data, however, one finds conflicting results. In one study, taking 8 grams once at the onset of symptoms appeared to decrease symptoms and duration of colds. In another, 10 gram doses were given for three days during a cold, without impact.

Obviously, when trying to measure the impact of any therapy on the progression of an illness – particularly one as protean as the common cold – numerous co-factors can enter the equation. It would seem then that a thoughtful modern study of vitamin C – one that carefully considers the methodology of those conducted in the past – is still needed before we can be certain of its potential impact on the common cold.


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Had Pauling invested in proving his point in the lab after the publication of Vitamin C and Common Cold, perhaps we would have a better understanding of the immune function of this nutrient today. But Pauling felt vitamin C’s protective effects against the cold were not seriously debatable and that, for him, it was time to move on. The physicians, he believed, were set in their ways – a description he often used during the long argument over vitamin C – and it was pointless for him to spend too much of his time and energy trying to disprove them.

Indeed, in Pauling’s mind, there were more important issues to take into the lab than the common cold. Because Pauling wasn’t just busy arguing that vitamin C could cure the common cold. He believed that it might cure cancer, too.

 

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.

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An Interview with Balz Frei, Director of the Linus Pauling Institute

Balz Frei

Balz Frei

Oregon State University is turning 150 years old in 2018, and already several projects are being developed to mark the occasion.  One of them is a major oral history initiative that is capturing the stories of a wide array of alumni, faculty, staff, administrators and friends of OSU.

Several months ago, the project conducted an interview with Dr. Balz Frei, who has led OSU’s Linus Pauling Institute since 1997.  A Swiss native, Frei worked under Bruce Ames at UC-Berkeley before moving on to Harvard, the Boston University School of Medicine and, ultimately, Oregon State.

Frei’s research has always focused on the processes fundamental to human health. During his time in Berkeley, Frei became interested in vitamin C and met Linus Pauling. His later work has focused on oxidative stress and the role that it plays in atherosclerosis. He has also investigated arterial function and potential dietary compounds – including vitamin C – that might help prevent oxidation of LDL cholesterol.

Under Frei’s leadership, the Linus Pauling Institute has stabilized its funding base, hired several principal investigators and made substantial contributions to the published literature on subjects relating to nutrition and optimal human health.

In 2011 the Institute celebrated a major milestone with the completion of the Linus Pauling Science Center. This 105,000 square foot facility, built for $62.5 million, is the largest academic facility project in OSU history. Now housed in this new space, LPI continues to conduct research on cardiovascular and metabolic diseases, healthy aging, and cancer chemoprotection, and engages in public outreach through its Micronutrient Information Center and Healthy Youth Program.

Excerpts from Frei’s oral history interview, including his memories of meeting Pauling, his sense of Pauling’s vitamin C work, and his vision for the future of LPI, are included below the cut.

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