(This introduction, which provides a preview of some important points made in the book, contains no references. The

rest of the book is referenced according to the norms of scientific publication.)

Vitamin C and Cancer

In the early 1970s, a Scottish physician, Ewan Cameron, reported striking benefits in terminal cancer patients given high doses

of vitamin C. Linus Pauling, Nobel Prize winning chemist, Nobel Peace Prize winning activist, put his great prestige behind

Cameron’s use of vitamin C. Driven by Pauling’s endorsement, considerable public excitement developed about this treatment.

However, from the first, mainstream medicine had been dubious. That attitude hardened with the publication in 1979, 1983

and 1985, of negative studies carried out at the Mayo Clinic. Those studies used the randomized double blind methodology,

which today is regarded as essential in assessing the value of medical treatments. This method ensures that a study begins

with comparable treated and control groups and that neither patients nor researchers know who has received treatment and

who has received a placebo. This "blinding" of doctors and patients serves to remove the effects of hope and

expectation, which might otherwise distort evaluation.

Cameron, who was convinced that vitamin C produced important benefits in his patients, refused to carry out a placebo study

that would deny treatment to patients in the control group. While the reports presented by Cameron and his associates seemed compelling,

the treatment evidently failed to work at the Mayo Clinic. Skeptics felt that Cameron's less rigorous methods had produced

an illusion of treatment effectiveness. While there were other studies that supported his findings, these too lacked the

randomized double blind method. In the eyes of mainstream medicine, the negative studies at the Mayo Clinic destroyed

any possible value in Cameron’s claims. Case closed.

It would be hard to exaggerate the oblivion into which vitamin C therapy has sunk in mainstream oncology, or the contempt

and hostility with which Cameron and Pauling were regarded by oncologists at the end of this debate. It was felt that they

had refused to put their hypothesis to a proper test by objective methods. Because of their abandonment of scientific

standards, they had been led astray by their preconceptions. In spite of his great scientific stature, Pauling could be depicted

as one of those eminent megalomaniacs who make pronouncements about matters outside their competence. Perhaps his

enthusiasm for vitamin C had something to do with senility?

Like many students of this subject, I have rejected this judgement by mainstream oncology. There seems to be a large

element of the irrational in the decision to develop certain anticancer effects into therapies and to reject or ignore others.

There are many non-toxic but non-patentable agents (like vitamin C), whose value has been suggested by initial tests in the

laboratory or by anecdotal evidence. These therapeutic possibilities are generally ignored. Instead oncologists give their

attention to the development of certain favored kinds of treatments.

Mainstream oncologists think it worthwhile to continually tinker with dose levels, treatment schedules, and combinations

of conventional chemotherapeutic agents and radiation. They are also involved in testing the exciting new products of the

biotechnology industry. Both of these interests are understandable. The current efficacy of cancer treatments is the result

of an immense investment of time and money in learning how to best use radiation and chemotherapy. The new

products of the biotechnology industry are based on an ever deeper understanding of the fundamental biology of cancer. These products

have begun to provide impressive new therapies. There is a rational expectation that the technology which produces these new

products will lead to the definitive cure of cancers in the not too distant future. Nonetheless, both approaches ignore the existence of a large

number of non-patentable, relatively non-toxic, and inexpensive agents, which exhibit anticancer effects. The thesis of this

book is that this class of agents may hold great therapeutic potential, and that vitamin C (especially when used in combination

with other agents), is one of the most impressive examples.

My thesis is that mainstream medicine has failed to show a rational and appropriate interest in the possibilities offered by vitamin C. Such an

accusation might seem odd. After all, the central characteristic of mainstream medicine is supposed to be its relentless and

systematic rationality, rationality exemplified in the development of the randomized, double-blind study. This (at least

in principle), rigorously excludes the influence of prejudice and misperception and allows the coldly accurate evaluation of

treatments. However, if modern scientific oncology chooses to entirely ignore certain areas, they will never be illuminated

by this splendid methodology. The kind of anticancer agents exemplified by vitamin C fall in a medical blind spot.

Some of oncolog's aversion to vitamin C originates in the personal prejudices of physicians and researchers. For decades,

most oncologists, like the American medical profession in general, have displayed an intense distaste for things found on

the shelves of health food stores. This distaste might be sufficient to prevent consideration of many otherwise promising

anticancer agents. Oncologists might also feel that they would do their careers no good by taking up the development of

cancer therapies from such disreputable stuff as vitamins, minerals, and herbal medicines.

In other cases, agents lacking the stigma of alternative medicine are ignored because the positive reports on these agents are

decades old. The initial positive reports were never followed up and have fallen into complete obscurity. To my knowledge,

there are no oncologists systematically re-examining the cancer literature of the past sixty years, looking for inexpensive,

non-toxic anticancer agents whose promise might have been overlooked. Most practicing oncologists are terribly busy and

lack both the time and inclination to learn about anything besides standard practices in their field.

Above, I referred to the fact that naturally occurring agents such as vitamin C are not patentable. The widely used products of the

pharmaceutical industry are protected by patents that give their originator a monopoly for some years. This is the central

fact in the economics of drug development. If physicians can be convinced of the value of a drug, this monopoly gives its

producers enormous pricing power. This is manifested in the financial record. The pharmaceutical industry has been the most

profitable of all legal industries for many years. A single highly successful drug can bring billions of dollars to a pharmaceutical

company. This creates enormous incentives to foster the development and use of such drugs. This also provides enormous means

for carrying out such a program. Hundreds of millions of dollars are available for clinical trials and for the marketing that effectively

changes the prescribing behavior of doctors.

The net result of medical prejudice and economic forces is a powerful bias toward the development of some therapies, and

against others. An example of the first would be alpha-interferon, one of the first fruits of the new biotechnology industry. Its

development was spurred on by a modest amount of positive animal data, a tiny amount of positive clinical data, a great

deal of irrational enthusiasm, and the hope of a financial bonanza. This was an initially ineffective treatment on which very

large amounts of money were spent during the late 1970s and early 1980s. Because there was such a drive to see interferon

work, it was extensively tested until cases were found in which it did exert significant therapeutic effects. Alpha-interferon

finally found its profitable therapeutic niche and eventually made a great deal of money for its patent holders.

Vitamin C provides a prime example of an unlovable potential therapy, an ugly, unpatentable thing, off the shelves of the

health food stores. With its low price and low margins, it is a cancer therapy that could never produce pharmaceutical sized profits.

Accordingly, only relatively microscopic amounts of money have ever been spent developing vitamin C into a cancer therapy.

As will be described below, some special persuasion was required to make mainstream oncologists finally investigate the anticancer

properties of vitamin C.

In the last section of the book the history of interferon and that of other widely used anticancer therapies will be contrasted

with that of vitamin C and other non-toxic, unpatentable agents.

Perhaps some readers will be put off by the preceding paragraphs. These might be seen as evidence of an

anti-establishment bias and an irrational hostility to conventional medicine. Perhaps the author suffers from an uncritical

infatuation with alternative medicine and every unconventional therapy. I think a look at my book will show

that this is not the case. In evaluating the findings about vitamin C I have tried to be as tough minded and critical as possible,

while avoiding the unthinking dismissal of findings which are still tentative and not yet confirmed by the best methodology.

I will try to construct rigorous arguments based on published and peer-reviewed data. When such data is lacking and I

have to draw on evidence from other sources (e.g. non-specialist publications, non-peer reviewed symposia, etc)

this will be pointed out. I promise that proponents of vitamin C or of any other unconventional therapy, will be held to

the same standards as their opponents. While I recognize much that is admirable in Ewan Cameron and Linus

Pauling, they come in for substantial criticism below.

The prejudices of conventional oncology were first exhibited in a refusal to publish Cameron's work in medical journals. The

main clinical description of Cameron’s work with vitamin C was rejected by one of the major cancer journals with the

objection that it was "not of sufficiently high priority to warrant publication space". It is of interest to consider this description

in light of the contemporary situation in oncology.

In the early 1970s, advances in cancer therapy were even more desperately needed than they are today. Many of the

important agents now in use were unavailable. Survival rates were not increasing significantly for most cancers. Side

effects of therapy made treatment a wretched experience for many patients. It was not clear that much could be

expected from further development of conventional cancer therapies.

Ever since oncology progressed beyond the use of surgery, and acquired specific weapons against cancer (radiation

and chemotherapy), it has struggled with the limited selectivity of those weapons. More intense attack on a

cancer meant greater damage to the body which carried it. Oncologists were certainly thinking about ways of

targeting these conventional treatments more selectively and reducing collateral damage, but there was no immediate

prospect of these possibilities being realized. In this situation, it is difficult to understand how oncologists

could have been less than enormously excited by the prospect of a novel and essentially non-toxic means of treating cancer. If

vitamin C was working as Cameron said it did, indeed, if it worked at all, this must imply some fundamentally new mechanism

through which cancer could be attacked.

Ewan Cameron, a sober, conservative, respectable (and perhaps somewhat unimaginative) physician and cancer theorist, had

reported that a simple, non-toxic and inexpensive treatment could produce desperately needed benefits in advanced cancer patients.

The effects reported by Cameron and his associates, though described in a cautious and rational manner suggested the possibility of

attacking cancer through some novel biological mechanism. Still, conventional oncologists, even before the appearance of

any negative information, even before any apparent failure to replicate this work, had dismissed it.

If there had been some reasoned case against vitamin C therapy, this might have been appropriate. But there was

no a priori basis for denying the reality of the effects reported by Cameron et al. In the early 1970s, no one knew

enough biochemistry to decide that vitamin C could not act against cancer in the way Cameron had reported. Is it possible

that they could not take Cameron's work seriously because of the irrelevant fact that Cameron was using a vitamin, and that

the medical use of dietary supplements was not regarded as quite respectable?

Non-toxic anticancer agents have a special interest. Their lack of toxicity allows their relatively unrestricted combination.

This implies that through synergies and addition of effects, combinations of such agents might treat much more effectively

than any individual agent. As will be seen, there is support for this expectation. There is also evidence that the effects of

conventional cancer therapies can be enhanced by combination with these non-toxic agents.

Cameron and Pauling were able to publish their work in 1974 and 1975 in Chemical-Biological Interactions,

a respectable, but non-medical journal. These papers included a theoretical article about ascorbate and cancer and the main

account of their clinical experience with vitamin C. Publication in this journal was arranged by Pauling who still was held in the

greatest esteem by scientists.

When Cameron published his findings, there was already an accumulation of evidence suggesting that vitamin C might have

some relevance to cancer. It had been well established that advanced cancer patients had very low vitamin C levels and that

their deficit did not respond to supplementation with the vitamin in the same way as in healthy people. A small number of

studies had shown that vitamin C protected against the induction of certain cancers and vitamin C was known to have

some antiviral effects. (At the time it was believed that viruses might play a major role in human cancers.) Data of this kind

could not directly support Cameron’s therapeutic claims, but should have made oncologists more receptive to the possibility

they were real.

Mainstream American oncologists never spontaneously and independently chose to try to replicate Cameron’s work. The

attempts to reproduce his findings occurred only when Linus Pauling made this happen by using all of his prestige and going

outside of normal channels. Pauling finally succeeded when he applied his considerable powers of persuasion to a senior

official at the National Cancer Institute. The decision to fund and carry out such a study was due to this individual. It did not

come about as the choice of oncology researchers or through the normal grant funding process.

The main report of Cameron’s clinical experiences appeared in 1974. Five years were to elapse before the first attempt to

replicate his work was published in 1979. During this period granting agencies refused to fund Pauling’s many applications to study

vitamin C’s effects on cancer in animals.

I will try to convey the compelling quality of Cameron’s clinical evidence within the compass of a few paragraphs, by

describing some of his most striking case histories.

A patient with an advanced and rapidly progressing cancer identified as a "reticulum cell sarcoma", was treated with high

dose vitamin C. Within ten days of beginning treatment the patient appeared almost free of his disease and then went on to

a complete recovery. The presence of the cancer had been verified before treatment by removal of a lymph node for

examination. A complete X-ray series documented the course of this patient’s illness. When the reports describing this patient

were submitted for publication, this evidence was repeatedly examined by independent experts who confirmed the diagnosis and

the occurrence of a remission.

When this patient appeared to be recovered, and about a month after vitamin C administration had been tapered off, his

cancer reappeared. Vitamin C administration was resumed and although the effect was slower the second time and larger

amounts of vitamin C were required, a second remission was obtained. This case constitutes impressive evidence. Advanced

cancer patients almost never spontaneously recover. The patient’s remissions were clearly linked in time to the administration

of vitamin C, as was the relapse when vitamin C was discontinued. While remarkable, this patient’s history is not unlike those

of about ten percent of Cameron’s patients, who showed objectively verifiable tumor regressions. Though those remissions 

tended to be temporary, even with continued administration of vitamin C.

In a small number of cases, patients became very sick or died following vitamin C therapy. This was apparently because

vitamin C produced a rapid destruction of tumors with fever and hemorrhage from the tumor sites. This interpretation was

strengthened when following administration of vitamin C, a visible tumor on a patient's gums disintegrated, producing an

almost unstanchable hemorrhage. At autopsy, tumor tissue in this patient was found to be dead and easily scooped out.

It is difficult to imagine how such reports could have come to be written in the absence of real effects of vitamin C on cancer.

No one has suggested that Cameron and his associates made up what they reported or that they were susceptible to

hallucinations. The accounts of the lethal syndrome associated with hemorrhagic necrosis of tumors would not have come from

authors so bewitched by their hopes for vitamin C, that they reported imaginary benefits.

If we find the accounts of Cameron et al compelling, we might look for differences between the original study and the supposed

replications to explain the different outcomes. While there are no compelling candidates for such differences, there are certainly

possibilities. These will be evaluated when the Mayo Clinic studies are discussed in later chapters. The utterly different effects reports

by Cameron and the Mayo Clinic (aside from differences in survival), strongly suggest that something was happening in Cameron’s

patients which did not happen in patients at the Mayo Clinic.

In addition to vitamin C effects on survival, Cameron et al reported dramatic palliative effects that reversed some of the symptoms

of advanced cancer. One of the most important of these symptoms is cachexia (pronounced "cakexia"). This is a relentless

wasting of fat and muscle, which continues even in the face of an increased intake of calories. It is accompanied

by disturbances of appetite, fatigue and muscular weakness.

Cameron and his associates reported that some advanced cancer patients given high dose vitamin C gained weight, felt better,

experienced improved appetite, improved strength and mobility, and sometimes dramatic relief of pain, especially from bone

metastases. When these effects failed to appear in a dramatic way in the Mayo Clinic studies, it was easy for conservative

critics to believe that these palliative effects were just another delusion afflicting wild eyed vitamin C enthusiasts. But in fact

there is abundant published confirmation of these palliative effects. Similar effects have been reported by the small number of physicians

who followed Cameron in using vitamin C against cancer. They were also often reported a generation earlier in the

German language medical literature. The similarity of these reports to those of Cameron et al is striking. Clearly, the

earlier German language reports reflect an entirely independent discovery of these effects. It seems inconceivable that

these could represent identical delusions, which independently sprang up in the absence of real palliative effects.

Palliative Effects and Severe Vitamin C Deficiencies in Advanced Cancer Patients

As was mentioned above, advanced cancer patients often show extremely low vitamin C levels. It has long been known that

such patients respond differently to the administration of large amount of vitamin C than do healthy controls. Normal people

start losing vitamin C into the urine when intake is modestly increased above the recommended daily amount (RDA).

This does not happen with advanced cancer patients. They may retain, and presumably utilize, grams of the vitamin. It seems

plausible that some of the symptomatic benefits of vitamin C in these patients might result from normalization of vitamin C levels,

and from matching supply to increased utilization. While this deficiency condition may be a sign of severe general debility rather

than a specific symptom of cancer, its presence surely should be of interest to oncologists.

One explanation of the reduced vitamin C levels seen in advanced cancer patients is that their cancers are taking up and

accumulating large amounts of the vitamin. While there is only limited evidence about this topic, this could be another way in

which vitamin C is critically linked to cancer. Because cancers typically are rapidly growing, they can be expected to have

exceptional requirements for vitamin C. This could also explain why vitamin C has sometimes shown pro-carcinogenic

effects and why experimentally induced vitamin C deficiencies have sometimes restrained the growth of cancers.

An explanation favored by the Cameron-Pauling camp, was that deficiencies in advanced cancer, represent the

exhaustion of vitamin stores used by the immune system to fight cancer.

The attempts to replicate Cameron’s work at the Mayo Clinic used the randomized double blind methodology. As was

mentioned above, one of the essential functions of this method is ensuring that the groups chosen to receive treatment or

placebo are equivalent. This is accomplished by randomly assigning subjects to each group from a single common pool of

subjects. Since Cameron et al had failed to use this methodology, skeptics explained their apparently positive findings with

the likely non-equivalence of those groups. The controls used by Cameron and Pauling were chosen to resemble

the treated subjects as much as possible. However, because the two groups had not been randomly selected from the same

pool of subjects there couold be no certainty they were equivalent. The significance of this random selection of control and

treatment groups is explained in Chapter Three which discusses methodological issues.

From the skeptics’ point of view, the patients selected for treatment could have been healthier to begin with, indeed, must

have been healthier to begin with. After all, the Mayo clinic studies had proved that there was no real vitamin C action against

cancer. Cameron and his associates, not realizing that somehow healthier patients were being selected for treatment, were

fooled into believing that vitamin C made their cancer patients better. This is the obvious thought, and has been unthinkingly

expressed by almost every critic of Cameron’s work.

But in fact, the data tell us that the time since initial diagnosis for the treated patients was about 20% longer than controls

at the point when the two groups were compared. This suggests that on average the treated patients should have been sicker

than the controls rather than healthier.

There is a much more serious difficulty with the critics interpretation. In their most cited papers, Cameron and Pauling

presented the outcome of vitamin C treatment quantitatively, describing the relative survival times of treated patients and

controls. These most cited papers provided no description of the clinical history of individual patients responding to vitamin

C and these clinical histories are something that the critics do not seem to have thought about. But these clinical reports

argue strongly against the critics’ interpretation. These reports do not tell us that the treated subjects showed the same

kind of decline as the untreated patients, but were merely later in doing so. Rather clinical reports tell us that many

of the treated patients showed striking improvements in their condition, (within subject changes), time locked to

the administration of vitamin C. These striking improvements often marked the beginning of surprisingly extended

periods of survival.

In the light of these clinical histories, it makes sense to regard enhanced survival in the treated group as a real effect, rather

than an artifact of biased subject selection. It doesn’t seem that the critics had read the clinical reports or had thought about

them. There seems to be something mechanical about the critics response. Cameron’s work was not methodologically

correct, so it was dismissed out of hand. There was little thought whether the methodological problems could realistically

have produced the very large reported anticancer effects as artifacts.

"in vitro" literally means "in glass", and refers to the culture of cells in a laboratory vessel. Cancer is often studied in this simplified

situation as well as in experimental animals ("in vivo"). It is accepted that the results of such studies will generally apply to human

cancers. Over the past three decades reports have accumulated that by itself or in combination with other agents, vitamin C has

anticancer effects in vitro and in experimental animals. While there are negative studies and while vitamin C has sometimes shown

pro-carcinogenic effects, there is no question that vitamin C has displayed a range of anticancer actions in these model systems,

and this supports a search for those same effects in human patients.

Of particular interest are studies indicating that vitamin C can produce "cytotoxic" (cell killing) effects like those of conventional cancer

therapies (e.g. chemotherapy and radiation), but here, selectively directed against cancer cells. This implies the absence of the severe

side effects associated with conventional cancer therapies. These cytotoxic effects in model systems certainly cannot explain all of

Cameron’s results because they require higher concentrations than Cameron would have produced when he administered

ascorbate orally rather than intravenously. In these cases, positive results would have to be explained on some other basis,

e.g. immune system stimulation or making tissues less susceptible to invasion by cancers.

Conventional anticancer therapies often owe their cell killing effects to the creation of free radicals and pro-oxidant conditions.

Vitamin C and related compounds can reduce toxic side effects of cancer therapies through their free radical scavenging

and antioxidant properties. On the other hand, oncologists have worried that this same protective mechanism could prevent

the killing of cancer cells by conventional therapies.

In fact, the published evidence shows that in many circumstances there is synergy between vitamin C and conventional

therapies. While it is possible for vitamin C to block the therapeutic effects of conventional therapies, it more frequently

enhances them.

A rebirth of vitamin C therapy for cancer

There is a small group of researchers at the Bio-Communications Research Institute in Wichita, Kansas, who have not only

continued to use Cameron’s therapy, but have worked to put this on a solid scientific foundation. In spite of the limited

resources available to workers in this area, they are generating convincing evidence about the effectiveness of the treatment

and about its mechanism of action. Some of their work has been published in a prestigious mainstream journal and they seem

to have a chance of successfully communicating their views to the larger scientific community.

Very recently, in September, 2005, a report was published in the prestigious journal Proceedings of the National Academy of

Sciences (USA) by a group lead by the eminent vitamin C skeptic Mark Levine. This report announced to great fanfare, that

high dose vitamin C, could selectively kill cancer cells. This report confirmed decades of long ignored research that had

reached the same conclusion. Because of the publication of this report, it is now much more probable that there will be a rebirth

of vitamin C treatment of cancer.