Cancer and Vitamin C: Crossroads of New Research

[Part 9 of 9]

In 2018, a third edition of Ewan Cameron and Linus Pauling’s book, Cancer and Vitamin C, was published. Released nearly a quarter century after Pauling’s death, this edition marked the first time that someone other than Pauling or Cameron contributed to the volume. The second edition, which was published in 1993, included an updated preface and a few new indices, but the text itself remained entirely Cameron and Pauling’s. The 2018 edition also includes a new preface and a new index, but both were written by Stephen Lawson of the Linus Pauling Institute at Oregon State University. Lawson used the new additions to ably present recent scholarship connecting the efficacy of vitamin C to the treatment of cancer.

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One bit of background that Lawson sought to clarify at the outset was the story of why vitamin C treatments for cancer had not been initially supported by outside research. As noted in our previous posts, Pauling and Cameron believed that external research corroborating their results would provide an effective avenue for convincing skeptics of the curative powers of vitamin C. The Mayo Clinic eventually agreed to conduct a study of this sort, but found that vitamin C did not improve cancer patients’ prognoses, and in some instances their outcomes were actually worse.

Even though Pauling and Cameron did not agree with the Mayo Clinic’s findings, they had a hard time making their case to the public about why the study was in error. But as described by Lawson in the 2018 preface, Pauling and Cameron recognized that the Mayo Clinic’s treatment protocols were different than their own in important ways. Specifically, Cameron and Pauling had always delivered vitamin C intravenously, whereas the Mayo Clinic researchers dosed their patients orally. At the time, Pauling and Cameron could not prove why this should make a difference, but they believed that it was a key reason why the Mayo Clinic did not get positive results. While science could not confidently address this scenario in 1979 – or even in 1993 at the time of the second edition – by 2018 researchers had developed a much clearer idea of the importance of intravenous application.

Beginning in 1999, a team of researchers began actively exploring the absorption of vitamin C and, in particular, whether or not there was a difference between oral and intravenous applications. As they conducted their work, the group discovered a previously unknown vitamin C transport molecule in the stomach, which helped to deliver ascorbic acid into the bloodstream. The team subsequently learned that there was an upper limit to how much vitamin C the transport molecules could carry. This effectively meant that no matter how much vitamin C a person ingested orally – vitamin C that would end up in the stomach – only a finite amount could actually be absorbed and utilized, due to the limited carrying capacity of the transport molecule. The exact amount of vitamin C that a transport molecule can carry is still being researched, with data to this point indicating that quantities may vary based on factors such as age.

In tandem with this discovery, researchers were also interested in understanding what happens when vitamin C enters the bloodstream, be it intravenously or through transport molecules in the stomach. As Lawson notes, studies found that one byproduct of high levels of vitamin C in the bloodstream (regardless of how it got there) is hydrogen peroxide. Hydrogen peroxide has the ability to fight cancer by altering its DNA, robbing its cells of ATP (the “muscle” of the cell), and fatally damaging its energy-producing mitochondria. When deployed at scale, this three-pronged attack might be presumed to fight cancer very effectively.

That said, hydrogen peroxide therapy has not been used with cancer patients, because there is no safe and effective way to deliver the substance into the bloodstream without damaging other healthy cells. While the connection between vitamin C dosing and internal hydrogen peroxide production is not well-understood, these preliminary findings suggest that high blood concentrations of vitamin C could create hydrogen peroxide in sufficient quantity as to be effective at neutralizing cancer cells.

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Several other new areas of research were highlighted in the 2018 edition, including the connection between vitamin C and hypoxia inducing factor (HIF). Some cancer tumors grow so fast that blood vessels cannot be created quickly enough to deliver oxygen to the expanding mass. To compensate for this lack of blood vessels in these hypoxic (or low oxygen) environments, tumor cells induce HIF, which stimulate the growth of blood vessels within the tumor. This inducement of HIF allows fast-growing tumors to continue to propagate and wreak havoc, rather than succumbing to oxygen starvation. For reasons that remain unclear, when vitamin C is introduced into a fast-growing tumor it represses the activation of HIF, compelling the tumor to remain in its hypoxic state and eventually die.

Emerging research on the relationship between vitamin C and dehydroascorbic acid (DHA) is also included in the 2018 edition. DHA is an oxidation product of vitamin C, and when present has been shown to reduce the amount of colorectal cancer in the body.

A collection of sixteen relatively recent clinical trials are likewise surveyed in the book, all of which examined the outcomes of different kinds of cancer patients when given vitamin C in conjunction with other chemotherapeutics. All sixteen found that patients’ outcomes improved once they were given the vitamin C in concurrence with their chemotherapy treatment. Five other studies were conducted on cancer patients given vitamin C but not chemotherapy. Results of these trials were mixed but, as Lawson points out, the non-chemotherapy researchers were primarily interested in determining optimal doses of vitamin C and measuring how quickly patients depleted their vitamin C infusions. Many of the trials also found that patient outcomes improved.

As with the original text of the book, a collection of case studies were also discussed by Lawson. And though they serve mostly as anecdotal evidence, Lawson shows that significant improvements in patients’ health have been documented once they have been administered vitamin C treatment.

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One of the biggest takeaways that a reader might glean from the 2018 edition is that, even though a significant amount of research has been conducted on the vitamin C and cancer connection, medical practitioners have been hesitant to deploy the treatment because the studies have seemed less than rigorous, or because other practitioners have found that it does not work with their patients. Lawson counters these sentiments by noting that most cancer research is novel and that only the most promising ideas go on to clinical trials. Further, because an optimum vitamin C dose has not yet been codified, doctors commonly administer vitamin C on an ad hoc basis. Worse still, doctors also sometimes administer the treatment as a “last ditch” effort after chemotherapy and all other treatments have failed. Pauling and Cameron demonstrated in their first edition that vitamin C needs to be administered continuously and before chemotherapy to be maximally effective. Clearly much remains to be done before the work that Pauling and Cameron started with their first edition can be called complete.

Cancer and Vitamin C: The Mayo Clinic Trial

Linus Pauling, 1979

[Part 7 of 9]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling sought to explore the potential for vitamin C to treat or even cure a disease that claimed the lives of millions per year. The two understood that many would raise an eyebrow at the notion that something as simple as vitamin C could treat cancer more effectively than other chemotherapeutics, and to defray this skepticism the duo knew that their point of view needed be independently verified.

After a period of reluctance, Pauling and Cameron found scientists at the Mayo Clinic who were willing to conduct a vitamin C trial on some of their cancer patients. But as we will see, instead of validating Pauling and Cameron’s findings, the Mayo Clinic’s results indicated that vitamin C did not help fight cancer, and in some instances, actually made patients’ outcomes worse. These findings were not at all expected by Pauling and Cameron, and afterward they devoted significant energy to unraveling what had gone wrong with the trials. But before they were able to do so, word had already spread that vitamin C did not work, and little that Pauling and Cameron did could change people’s minds from there.

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Ewan Cameron was a physician at Vale of Leven Hospital in Scotland who, after reading up on the subject, and believing that he had nothing to lose, began to treat some of his most severe cancer patients with vitamin C. The results were quite dramatic, with some patients who were near death making positive progress that bordered on miraculous. Even though many of the treated patients’ cancer was so progressed as to rule out a complete recovery, nearly all those given vitamin C experienced a marked improvement of their quality of life. Cameron was convinced and soon almost all of his cancer patients were being given vitamin C.

Shortly after Cameron began vitamin C treatments in earnest, he began his collaboration with Pauling. The two knew that their results had the potential to change medicine and they were eager to let the scientific world know about the work. The problem, however, was that no clinical trial or scientific study had been conducted, and the team knew that claims based on anecdotal data would not hold up in the eyes of many. One solution would be for Cameron and Pauling to conduct their own trial, but Cameron objected to this on moral grounds, believing it wrong to treat a portion of the trial group with a placebo instead of life-saving vitamin C. As such, Cameron was unwilling to conduct a clinical trial on his own patients. Pauling supported his partner’s stance but still understood the need for someone to validate their results.

Cameron and Pauling were also aware of the difficulties inherent to convincing a research group to undertake such a task, particularly given the unorthodox nature of their claim. For many, vitamin C also seemed too simple and too easy a solution. Notably, Cameron and Pauling were likewise not able to readily explain how vitamin C worked. They knew that the treatment did work because they had seen it do so in patient after patient, but the actual underlying biological mechanism remained elusive.

Another problem that Cameron and Pauling faced was the fact that ideal vitamin C dosing had not been formally determined. In other words, there was no standard dose of vitamin C for Cameron’s cancer patients. Instead, Pauling and Cameron let individual patients’ bodies “decide” their own specific optimal dose. They did so by increasing individual dosages up to bowel tolerance — once a patient began experiencing diarrhea, they had reached their maximum dose. This lack of uniformity was atypical and looked down upon by many.

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Though Pauling and Cameron were in need of their own study, clinical trials that examined vitamin C and cancer had actually predated their work. The earliest study that Cameron and Pauling were able to find took place in Germany in 1940, several decades before Cameron began dosing his patients with vitamin C. In the German study, researchers confirmed that cancer patients tended to have lower levels of vitamin C in their blood than was the case with healthy subjects. Much later, in 1979, a Japanese team found that cancer patients who were given vitamin C tended to enjoy better five-year prognoses compared to those who did not add supplemental vitamin C to their diets.

These data, while helpful, mostly left Pauling and Cameron wanting more. What they needed was research that mirrored their own approaches to treatment and that would help support their ideas. Through some advocating by Pauling, scientists at the Mayo Clinic in Minnesota agreed to conduct a study that intended – but ultimately failed – to mimic Cameron and Pauling’s work. Carried out in 1978-1979, the study was double-blind, meaning that patients and practitioners alike could not determine if a given participant was in the treatment group or the placebo group.

At the conclusion of the study the Mayo researchers published their results, and they were not what Pauling and Cameron had hoped for, nor expected. Instead of finding that vitamin C helped fight cancer, the Mayo study concluded the polar opposite, going so far as to advocate that vitamin C not be used in conjunction with a cancer patient’s therapy.

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Pauling and Cameron were both scientists at their core and would have been willing to accept the Mayo results if they thought that the trials had been rigorous. But in fact, Pauling and Cameron believed that the Mayo Clinic’s study was too dissimilar to their own protocol to be considered a valid test. Notably, the duo objected strongly to the fact that patients in the Mayo study were given vitamin C after receiving chemotherapy, whereas Cameron and Pauling always gave vitamin C before chemotherapy. This was important because Pauling and Cameron believed that chemotherapy degraded the effectiveness of vitamin C and, as such, dosing afterwards was bound to yield poor results. Indeed, in their own work, Cameron and Pauling had developed similar conclusions to the Mayo team for patients given vitamin C after chemotherapy. Fundamentally, Cameron and Pauling were not trying to prove the effectiveness of vitamin C when used after chemotherapy, but before.

Cameron and Pauling also balked at the trial’s method for administering vitamin C. Importantly, in the Mayo study, patients were given vitamin C orally, whereas Cameron and Pauling delivered their doses as intravenous drips. Even though Cameron and Pauling did not, at the time, know for sure why the mechanism of delivery should make a difference, they clearly understood that it did. The Mayo group disagreed and argued that their testing protocols were similar enough that the results should be deemed as valid.

In the end, the Mayo Clinic’s prestige and name recognition won out, and most observers aligned themselves with the study’s results. And while this clearly affected physicians and their prescribing behavior, it did not diminish Cameron and Pauling’s belief in the efficacy of vitamin C to treat cancer, and they continued to advocate for its use.

Cancer and Vitamin C: Misnomers and More

Pauling at the chalkboard, 1979.

[Part 6 of 9]

Ewan Cameron and Linus Pauling’s 1979 book, Cancer and Vitamin C, was rooted in the most sound scientific understanding that could be compiled at the time. And through its three editions, many of the novel conclusions that the duo put forth made their way into the alternative health mainstream. That said, there are some assertions in the book – especially related to cancer treatments – that have been proven to be incorrect, and in places the authors use language that is certainly out of date.

Pauling and Cameron’s support of a synthetic estrogen, diethylstilbestrol (DES), is an area open to criticism. In their overview of cancer types and treatments, special attention was paid to cancers of the reproductive organs. This was so because, as Pauling and Cameron explained, reproductive cancers could sometimes be addressed with hormonal therapies. Certain breast cancers, for example, respond well to hormones and can be managed quite well with estrogen alone. Oftentimes these treatments were administered through the use of synthetic hormones, and one that Pauling and Cameron touted as being effective was DES.

First introduced in the late 1930s, DES developed a reputation as a miracle compound. It was used to help women overcome morning sickness during pregnancy, and doctors later deployed it to help prevent miscarriages. By the 1970s however, researchers were finding a correlation between treatment with DES and higher rates of birth defects. Despite these data, the connection, at the time, was somewhat ambiguous, and physicians continued to prescribe the drug. When Pauling and Cameron wrote their book, DES was also seen as a viable and effective treatment option for cancers, particularly of the breast and prostate, and Cancer and Vitamin C makes note of its safety and efficacy, particularly in addressing prostate cancer. Today however, adverse effects from DES are much better understood and, by 1997, manufacture of the hormone had essentially ceased.

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Pauling and Cameron also made references to cancer prediction that did not hold up. Certain of these references were hamstrung by the fact that the field of genetic counseling had not been fully established by 1979. In their discussion of women’s health, Pauling and Cameron recognized that there appeared to be a link between breast cancer and ovarian cancer, and that these diseases sometimes ran in families. It was believed, therefore, that there was a genetic component to these diseases, but the authors felt as though it would be a long time before much could be done about such cases.

Today, while genetic counseling cannot prevent cancer per se, certain gene mutations have been identified as posing more particular risks, and individuals who show markers for those mutations can take actions to improve their odds for staying healthy. Those with the BRCA mutation, for example, have a much higher chance of developing breast and ovarian cancer, but with enough advance knowledge they can elect into surgeries or enhanced screenings that can drastically reduce cancer risk. So while Cameron and Pauling were pretty clearly aware of these genetic links, their language suggests that they did not anticipate the role that genetic screening plays today.

Another misnomer related to cancer prediction has to do with Pauling and Cameron’s assertion that cervical cancer is not caused by an STD, despite other theories at the time that suggested as much. Fundamentally, the idea that a communicable disease could cause a noncommunicable disease did not seem to make sense to the duo. However, we know today that certain strains of viral hepatitis can develop into cervical cancer. This knowledge has resulted in a hepatitis vaccine that is essentially a cancer vaccine. Nothing of the sort was mentioned as a possible treatment option in the book, likely because the idea did not seem to be supported by the scientific evidence that Pauling and Cameron were consulting.

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Some of Pauling and Cameron’s misnomers were not directly related to scientific argument, but instead are more a reflection of the times in which the book was written. This is particularly evident in their olios of cancer patients who were treated with vitamin C. Part of their rationale in doing so was to humanize cancer and its treatment, especially with vitamin C. As a result, in addition to a description of their disease trajectory, Pauling and Cameron also provided a brief description of the person, including details like their age, job, and even physical appearance.

While these descriptions add personality to the text, they also offer a glimpse into the rhetoric of the day that is sometimes cringe-inducing, particularly when it comes to women. One patient, for example, was described as a “plump jolly widow,” another was a “slim attractive housewife,” and a third was a “wealthy attractive woman in her early forties.” In other instances, women were defined in terms of their husband’s occupations; the “wife of an unemployed shipyard laborer,” for example, and “the wife of a prosperous doctor.” In this, Cameron and Pauling’s cancer book also provides the reader with a document of cultural value, if unwittingly.

Cancer and Vitamin C: A Review of the Book

The Camerons and the Paulings in Scotland, 1974

[Part 5 of 9]

Cancer and Vitamin C, by Ewan Cameron and Linus Pauling, was first published in 1979. A second edition was released in 1993, and a third came out in 2018. While the later editions included new ancillary materials, the primary text of the book mostly remained unchanged. In it, Pauling and Cameron fundamentally sought to make the case that vitamin C therapy is an effective means of treating cancer; indeed, even more effective, in some cases, than “traditional” therapeutics. In building these claims, the book outlines the ways in which vitamin C helps to fight cancer on both theoretical and metabolic bases, and concludes with specific examples of therapeutic successes.

Even though the book was written by a Nobel laureate (Pauling) and a leading cancer physician (Cameron), the text is approachable for a general readership. The book’s short chapters help maintain a quick pace while allowing for discussion of many topics without getting overly detailed. But in part because of this structure, the authors do not fully explore the connection between vitamin C and cancer until about halfway into their text. The initial chapters are instead devoted to establishing a foundational understanding of cancer and disease, thus equipping the reader to more fully appreciate how vitamin C might related to cancer. Once the connection is made however, the book approaches vitamin C and cancer from so many different angles that it is hard to finish without at least considering the value of a prophylactic vitamin C supplement.

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The book begins with an overview of cancer and carcinogens, notably including heat. In their text, Pauling and Cameron make reference to higher incidences of cancer among people who use coals to heat their body, as was practiced in India and elsewhere. Pauling and Cameron believed that the heat was somehow changing individuals’ DNA, and that this was contributing to the higher cancer incidence. This assessment, of course, was informed by Pauling’s understanding of how other carcinogens, such as radiation, caused cancers and birth defects in those exposed. The notion that cancer could be the result of DNA changes was a novel idea at the time of publication, and the understanding that chromosomal changes could occur as a result of radioactive carcinogens was also relatively new. Nonetheless, Pauling and Cameron suggested that many incidents of cancer could be a result of changes to or mutations in DNA.

From there, the authors focused on a discussion of the various types of cancer, classifying each by the area of the body that is affected. Accordingly, the book contains unique discussions of cancers of the skin, stomach, esophagus, larynx, pancreas, liver, gallbladder, bladder, and lung. Cancers of the sexual organs (testicular, ovarian, prostate, uterine and breast) were given particular attention because, according to Pauling and Cameron, hormones usually affected these in particular ways that played a key role in the effectiveness of vitamin C treatment. Cancers of the lymphatic system, sarcomas (tumors of the bone), tumors of the brain, tumors of the blood, and tumors in infants were also explored in the book.    

Following this discussion, Pauling and Cameron shifted their focus to the common kinds of cancer treatments that one might expect to receive, including surgery, radiation, chemotherapy, hormones, and immunotherapy. Once again, little attention was paid to vitamin C in these early chapters. Instead, the authors chose to detail more conventional treatment options as a means to developing a common understanding with the reader.

One interesting exception to this approach was the duo’s discussion of chemotherapy. As will be examined in later posts, independent researchers found that patients given vitamin C fared no better than their counterparts who were not given vitamin C. Pauling and Cameron protested these results, in part because the patients in the independent study had received chemotherapy followed by vitamin C treatment. Pauling and Cameron argued that chemotherapy works by destroying the immune system and vitamin C works by strengthening it. Logically then, vitamin C therapy would be most effective in instances where patients have not received chemotherapy.

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After setting this groundwork, Pauling and Cameron then began to explain why vitamin C was an ideal substance to treat cancer. The specifics of their argument are detailed in our previous posts, but in general, vitamin C was believed to be effective against cancer because of its ability to enhance the immune system’s natural defenses; essentially it boosted the fighting power of the immune system. Pauling and Cameron drew these conclusions through human trials, literature reviews, and anecdotal evidence, and ultimately argued that vitamin C should be used in conjunction with nearly every cancer patient’s treatment protocol, and sometimes even in lieu of orthodox treatment altogether.

Pauling and Cameron concluded the book with a discussion of other people’s research; specific examples of people who had been treated with vitamin C; and analysis of clinical trial results. Each of the editions winds up with a series of appendices relaying, for example, the estimated number cancer deaths in the United States at the time of publication; information about various anti-cancer drugs and their chemical method of action; and, later on, the details of an important symposium on vitamin C and cancer, which we will review in a later post.

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Cancer and Vitamin C is ambitious and full of complicated scientific and medical concepts that the authors explain in terms understandable to most readers. Amidst it all, the authors’ message is clear throughout the book: vitamin C can help to cure cancer and should be used. While the first part of the volume initially appears to be a bit off topic, readers are rewarded later with a rich connection made between the nature of cancer and the value of vitamin C. And whether or not the reader accepts the book’s central thesis, its thorough explanation of cancer as a disease and of terms associated with cancer will prove beneficial to many.

Controversial from the moment that it was published, Cancer and Vitamin C remains compelling today, a worthwhile investment for skeptics and believers alike. And for those interested in Linus Pauling as an individual, the book provides valuable insight into how his ceaselessly curious scientific mind could take an issue as perplexing as cancer and approach it in a classic Pauling way: different from his peers and with a keen sense of intuition.

Optimal Health and the Synthesis of Vitamin C

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

[Reading Cameron and Pauling’s Cancer and Vitamin C, part 4 of 9]

In their ambitious 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling argued that vitamin C possessed the ability to cure cancer. As remarkable as this suggestion was, in some respects it was almost secondary to the broader biological role that Pauling and Cameron assigned to the vitamin. As they made clear in their book, much of vitamin C’s importance could be attributed to the special way that it is made by most animals…not including ourselves.

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As animals, including humans, have evolved, they have lost the ability to internally synthesize certain vital nutrients, which must now be obtained through diet alone. That said, nearly every being in the animal kingdom has retained the ability to synthesize its own vitamin C. In fact, humans are among a very small subset of animals who have lost this ability over evolutionary time, such that all of our vitamin C needs must now be met through diet. If a person does not meet this dietary need, they will develop scurvy, grow sick and eventually die. Therefore, it is paramount that humans regularly consume a baseline amount of vitamin C.

In addition to vitamin C, humans also cannot synthesize vitamins A, B1, B2, B6, and niacin, all of which are also essential for life. A deficiency in niacin, for example, can lead to pellagra, a primary disease of the skin which can result in death. Likewise, a deficiency in vitamin B1 can manifest as beriberi, a potentially fatal disease of the nervous system. But even though the absence of these nutrients will usher in dire consequences, humans have lost their ability to produce them internally.

Why is this so? The basic prevailing theory is that even though these nutrients are vital for life, food-based sources have historically been so plentiful that there was no need for the nutrients to be produced “in house.” Moreover, from an evolutionary perspective, obtaining a nutrient from a food source, rather than through self-synthesis, offers significant advantages, since it can require a lot of energy to internally produce nutrition. Once freed from the burden of self-synthesis, an organism becomes capable of applying that store of energy toward other activities.

But vitamin C seems to be a special case. Despite the evolutionary advantages of obtaining nutrition from food sources, every studied animal on Earth continues to synthesize it internally except for the following: humans, primates, guinea pigs, one species of fruit eating bat, a South Asian bird called the red vented bulbul, some grasshoppers, and fish in the trout family. For Pauling and Cameron, the tenacity with which animals have held on to the ability to produce their own vitamin C was further proof of its importance.

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So again, why not humans too? Why have we lost this ability? Pauling and Cameron believed it was due to an evolutionary quirk.

As we have noted, there are evolutionary advantages to losing the ability to synthesize vitamin C. If two animals are competing for resources, the animal that is not also preoccupied with the internal process of generating its own nutrition will theoretically outcompete an opponent that is hamstrung with that energy burden. Pauling and Cameron believed that, at some point in the past, a mutant human ancestor who could not synthesize its own vitamin C successfully outcompeted other human ancestors, and was able to do so because, at that time – around 50 million years ago – its environment was abundant in vitamin C-rich foods. As the mutant bred and passed along its genetics to its progeny, its traits continued to outcompete, out-mate, and eventually eliminate vitamin C-synthesizing humans altogether. Pauling and Cameron posited that a similar situation arose with other animals, including primates, who have also lost their ability to synthesize vitamin C.

And while that idea makes intuitive sense, one still wonders why nearly all other animals have retained their capacity for vitamin C synthesis, even while losing the ability to internally produce other nutrients. The answer, according to Pauling and Cameron, is two-fold. Point one is that vitamin C is objectively important, and this special importance meant that animals tended to retain the ability to synthesize it. Crucially for humans, point two is that animals’ true need for vitamin C is far greater than what can be obtained through diet alone. In this sense, even though the human mutants were able to outcompete their synthesizing foes for a time by obtaining vitamin C through diet, maintaining that diet was not sustainable for a growing population, and perhaps the mutants never truly obtained enough vitamin C after all.

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Pauling and Cameron were convinced that humans were underdosing their vitamin C, and doing so in part because of the guidance being provided by the very agency charged with providing accurate information on nutritional needs. The Recommended Daily Allowance (RDA) provided by the United States Food and Drug Administration (FDA) serves as a standard for the amount of a given nutrient that one should consume per day to maintain their health. Pauling and Cameron believed that the RDA chronically underestimated the true daily needs for specific nutrients; the recommendation for vitamin B1, for example, was about 1.5 times below optimum in their minds. In the case of vitamin C however, Pauling and Cameron believed the RDA to have been grossly underestimated at about 200 times below optimum daily need. Where once the FDA was recommending 60 mg of the nutrient per day, (bumped up to 90 mg in the year 2000) Pauling and Cameron pushed for 12,000 mg.

To determine the optimal dose of vitamin C for humans, Pauling and Cameron looked at how much vitamin C other animals synthesize, and how much dietary C the mutant human ancestor might have been expected to consume on a daily basis. For this second supposition, the researchers used data on how much vitamin C is present in specific foods and what types of foods were likely predominant when the mutant edged out its competition. The outcomes of this analysis connected with observations of contemporary primates who live in climates similar to the mutant and who ingest large amounts of vitamin C daily through their diets — volumes close to the 12,000 mg that Pauling and Cameron believed to be ideal. Finally, when analyzing the amount of vitamin C that other animals synthesize, a conjecture can be drawn about the optimal quantity for humans. A 154 pound goat, for example, could be expected to synthesize 13,000 mg per day, and other animals generated quantities that were roughly proportional to the goat by body weight.

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For Pauling and Cameron, the evidence from the animal kingdom further compounded the idea that vitamin C is vital for life and that large amounts of the substance are crucial for maximizing health. But because we have lost our ability to produce our own vitamin C, most humans are living in states of suboptimal health and are exposing themselves to greater risk of affliction with serious disease. And because – as we saw in our previous post – the symptoms of scurvy closely mimic those of cancer, one might draw a connection between the two, and posit that biologically insufficient vitamin C levels are a source for increasing rates of cancer.

Why Vitamin C? The Scurvy Connection

James Lind

[Reading Cancer and Vitamin C, part 3 of 9]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling made clear that vitamin C was uniquely suited to fight cancer, but the duo still needed to address some unanswered questions. Namely, what was so special about vitamin C, and how did that specialness help it to fight disease?  For Pauling and Cameron, part of the answer was connected to vitamin C’s protective factor against scurvy.

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By the time that they were working on their book, it had been long understood that the body could store vitamin C. It was likewise well-known that, without any new infusions, these stores would deplete and symptoms of vitamin C deficiency would begin to manifest. Scurvy is the disease that arises once the stores have dropped below a critical level, with symptoms including drops in weight, loss of teeth, bleeding gums, poor wound healing, seizures, jaundice, disorientation, and eventually death. Scurvy was quite common among sailors because the food they took with them on their long voyages often lacked adequate levels of vitamin C. These foods, which were selected because they wouldn’t spoil, generally featured biscuits and cured or salted meats. But after months at sea, eventually their vitamin C concentrations would diminish, and disease would set in.

For a long while it wasn’t well understood what the exact source of scurvy might be, though many suspected it had something to do with one’s diet. As early as 1536, French explorer Jacques Cartier found that he was able to prevent scurvy by drinking a tea made from arborvitae leaves, which was great from a practical viewpoint but still didn’t unravel the root cause of the illness. Almost two centuries later, in 1747, Scottish physician James Lind initiated a concerted effort to uncover the secret. By manipulating the diets of scurvy patients, Lind soon discovered that those who were given an orange and a lemon were cured, while others who consumed diets lacking oranges and lemons continued to decline. But what exactly was in lemons and oranges that could help stave off scurvy remained a mystery.

Almost two-hundred years passed before the secret ingredient in oranges and lemons was finally unlocked, when Albert Szent-Györgyi isolated the substance in 1928 and correctly identified it as vitamin C in 1932. As a result of Lind’s discovery and Szent- Györgyi’s subsequent work, scurvy is now an entirely preventable disease.

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As they continued their review of the literature, Pauling and Cameron came to realize that there is also a connection between scurvy and cancer; a connection that was also made centuries earlier by James Lind. When Lind was conducting his scurvy work, part of his search for a cure involved performing autopsies on those who had died of the disease, and he was interested to find that many patients with scurvy also suffered from cancerous tumors. This intriguing connection between cancer and scurvy was not more fully explored at the time, because when people contracted scurvy, they typically died shortly thereafter, meaning that cancer was rarely their cause of death.

In 1954 however, a Canadian physician, W.J. McCormick, reached the conclusion that both scurvy and cancer were diseases of collagen, and that scurvy damaged cells in a manner almost identical to the changes wrought by cancer cells as they replicate. McCormick also pointed out that late-stage cancer symptoms are very similar to those of late-stage scurvy, including anemia, hemorrhaging, formation of ulcers, increases in infections, and low levels of plasma and leukocytes. These connections added weight to Pauling and Cameron’s belief that vitamin C held secrets to fighting cancer, and encouraged them to keep pressing their case.

Why Vitamin C? Cancer Fighting Properties

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

[An analysis of Ewan Cameron and Linus Pauling’s book, Cancer and Vitamin C. This is part 2 of 9.]

In their 1979 book, Cancer and Vitamin C, Ewan Cameron and Linus Pauling argued that vitamin C could be used to effectively treat cancer. With such a bold claim having been issued, vitamin C now needed to do a lot of heavy lifting. More specifically, Pauling and Cameron needed to prove that vitamin C could a) effectively treat cancer and also b) do so better than other substances being used to treat and cure cancer. As such, the authors devoted nearly half of their book to exploring vitamin C’s unique properties, with particular attention naturally paid to its cancer-fighting abilities.

In doing so, Cameron and Pauling first examined known cancer-causing agents on the cellular level and then investigated how vitamin C interreacted with these agents. One such substance was the enzyme hyaluronidase. When Pauling and Cameron were writing their book, it was widely recognized that certain malignant tumors released this enzyme and that, when exposed to healthy tissues, the enzyme would break down the glycosaminoglycans, which might be likened to the “cement” that makes tissues strong. As the cement became weaker, the tissues grew more vulnerable to being penetrated by cancer cells. By extension, it was believed that hyaluronidase promoted the spread of malignant cells within the body. It was also suspected that cancer cells released a different enzyme, collagenase, which would break down the collagen in tissues, further weakening cells and making them more susceptible to disease.

Having established this, Pauling and Cameron then illustrated the role that vitamin C could play in obstructing this process. Studies had found that vitamin C naturally helps to produce a hyaluronidase inhibitor, which in effect blocks the enzyme and stops the destruction of the tissue cement. Furthermore, vitamin C is known to be a necessary component for the building of collagen, and it was proposed that increased intake of vitamin C could boost collagen production and strengthen cells even more.

When Pauling and Cameron published their first edition, some of the ideas regarding hyaluronidase and collagenase were speculative. Pauling and Cameron were also relying on their collective scientific expertise to develop a model for vitamin C’s interactions with these enzymes. Pauling was not shy about making informed inferences to explain scientific phenomena, and in the case of vitamin C and these two enzymes, his thinking appears to have been correct. Since the publication of the first edition of Cancer and Vitamin C, two different research teams have published articles (in 2001, 2004, 2010, and 2011) which found evidence that vitamin C does in fact help to inhibit hyaluronidase.

More recent research has also suggested that high levels of vitamin C generate hydrogen peroxide. While it is not clear what the exact mechanism is that causes this, it is known that hydrogen peroxide can lead to a type of cell death that turns out to be useful in the cancer fight. Most healthy cells are not impacted by hydrogen peroxide because of the presence of an enzyme, catalase, that neutralizes its impact. Cancer cells, on the other hand, are not equipped with catalase; or if they are, the amount is negligible. So it is now well-established that hydrogen peroxide can kill cancer cells, but getting sufficient quantities of hydrogen peroxide to cancer cells inside the body has proven challenging. By administering large doses of vitamin C, it is hoped that clinicians may someday be able to provide targeted hydrogen peroxide therapy to patients who could benefit from it.

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While Pauling and Cameron were able to provide data-based connections between vitamin C and its ability to fight cancer, their book also includes more anecdotal ideas that support their argument. One such observation was that patients who were given vitamin C for cancer treatment tended to experience less severe side effects from chemotherapeutics than those who did not take vitamin C. Although it was hard to quantify, Pauling and Cameron noted several instances where bed-ridden patients under Cameron’s care would take vitamin C and soon be capable of moving about. Cameron also observed that patients who stopped taking vitamin C often saw their symptoms rapidly return.

More notably, several of Cameron’s patients who were given vitamin C were found to go into remission. Because of ethical concerns related to placebo trials, Cameron and Pauling did not have any controls to support their claims. However, many of the patients took no treatment other than vitamin C, and Cameron, who had been a practicing physician for many years prior to beginning work on vitamin C therapy, understood that remissions for many of these cancers was not at all common.

To further support the notion that there was something special about vitamin C, Pauling and Cameron also observed that healthy people could not tolerate as much supplemental vitamin C as could those suffering from cancer. That is to say, healthy patients could take only so much vitamin C before they began to experience side effects, such as diarrhea, than was the case with cancer patients. This anecdote suggested to the authors that cancer patients needed a large amount of vitamin C – all of it was, in effect, being used, and as such there were no negative side effects. In fact, the appropriate dosage was often determined by giving a patient as much as they could tolerate before experiencing side effects.

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Pauling and Cameron knew that vitamin C helped fight cancer. They saw that their patients were getting better and, from a molecular viewpoint, the mechanisms involved made sense, even if the data wasn’t in hand to prove everything. But there was more to support vitamin C as a model substance for treating cancer, and that had to do with its connection to scurvy, which we will explore in our next post.

Reading “Cancer and Vitamin C”

[An exploration of Ewan Cameron and Linus Pauling’s influential – and controversial – 1979 book. This introductory post is part 1 of 9.]

Despite all of the research that goes into cancer, relatively little progress has been made in its treatment — at least, that was the conclusion that Linus Pauling had arrived at in the 1960s. Long interested in the subject, Pauling was frustrated that many of the treatment options that had been developed helped to prolong life, but usually failed to cure disease.

As someone who often looked first to chemistry in his search for answers, Pauling increasingly came to believe that his growing interest in the power of vitamins might hold the key to not just treating cancer but curing it. By the 1970s, Pauling had teamed up with a key collaborator, Scottish physician Ewan Cameron, and in 1979 the duo published an important book titled Cancer and Vitamin C.

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Beginning in the 1960s, Pauling’s scientific gaze began to focus on the connection between the potential connection between optimal health and vitamins, and he eventually came to theorize that many diseases could be sourced to vitamin deficiencies. By extension, Pauling surmised that if a deficiency of vitamins could cause disease, then perhaps an increase in vitamins could help stave off or even reverse an illness. Doing so, however, was not merely a case of the patient taking a few supplements. Instead, Pauling reasoned that massive amounts of a vitamin were often necessary.

This approach to treating disease – commonly referred to as megadosing – blossomed into a new field, which Pauling labeled “orthomolecular medicine.” Convinced that this work had great promise, Pauling co-founded an institute devoted to advancing the research, much of which he and his collaborators published in both the scientific and popular literature. Orthomolecular medicine, in Pauling’s view, could help cure maladies ranging from the common cold to schizophrenia. And while many vitamins were of interest to Pauling, one in particular took on central importance: vitamin C.

In 1979, Pauling and Cameron completed work on Cancer and Vitamin C, a popular text in which the authors attempt to persuade their readers to agree with two basic ideas: one, that vitamin C is powerful enough to treat cancer; and two, that the treatment regimen they outline actually works. Over the next three weeks, we will explore Cameron and Pauling’s endorsement of vitamin C from three different angles. After that, we will dig into an analysis of the book itself, including important updates on new research that were incorporated into a 2018 reissue of the volume.

Pauling, Stanford and Research – Part 2

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.

Cameron and Pauling’s Attack on Conventional Views of Cancer

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.

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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.

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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.