© Whole Foods Magazine
The Science of Vitamin C and Cancer:
A Tribute to Linus Pauling and an Interview with Steve Hickey, Ph.D.
By Richard A. Passwater, Ph.D.
At this time of the year, it is always useful to discuss vitamin C and colds, but it is more important to discuss vitamin C and optimal health including treating cancer. This month, we have the opportunity to chat about vitamin C and various health topics including the recommended dietary allowances (RDA), cancer and optimal health. Also, recent studies have verified and validated what Dr. Linus Pauling knew and reported. Linus, you are not forgotten and your work was not in vain!
Before we chat with Dr. Hickey, three recent research publications need to be brought to your attention. The first item is a study done by Johns Hopkins researchers elucidating how vitamin C destroys cancer cells.
In mid-September, Johns Hopkins University issued a press release stating (1):
Nearly 30 years after Nobel laureate Dr. Linus Pauling famously and controversially suggested that vitamin C supplements can prevent cancer, a team of Johns Hopkins scientists have shown that in mice at least, vitamin C—and potentially other antioxidants—can indeed inhibit the growth of some tumors… The Hopkins study, led by Chi Dang, M.D., Ph.D., professor of medicine and oncology and Johns Hopkins Family Professor in Oncology Research, unexpectedly found that the antioxidants’ actual role may be to destabilize a tumor’s ability to grow under oxygen-starved conditions. Their work is detailed this week in Cancer Cell.
“The potential anticancer benefits of antioxidants have been the driving force for many clinical and preclinical studies,” says Dang. “By uncovering the mechanism behind antioxidants, we are now better suited to maximize their therapeutic use.”
“Once again, this work demonstrates the irreplaceable value of letting researchers follow their scientific noses wherever it leads them,” Dang adds.
Drs. Gao and Dang suspected that a mechanism involving a protein known to be dependent on free radicals called HIF-1 (hypoxia-induced factor), which was discovered over a decade ago by Hopkins researcher and co-author Dr. Gregg Semenza, director of the Program in Vascular Cell Engineering. Indeed, they found that while this protein was abundant in untreated cancer cells taken from the mice, it disappeared in vitamin C-treated cells taken from similar animals.
“When a cell lacks oxygen, HIF-1 helps it compensate,” explains Dang. “HIF-1 helps an oxygen-starved cell convert sugar to energy without using oxygen and also initiates the construction of new blood vessels to bring in a fresh oxygen supply.”
Some rapidly growing tumors consume enough energy to easily suck out the available oxygen in their vicinity, making HIF-1 absolutely critical for their continued survival. But HIF-1 can only operate if it has a supply of free radicals. Antioxidants remove these free radicals and stop HIF-1, and the tumor, in its tracks.
The researchers confirmed the importance of this “hypoxia protein” by creating cancer cells with a genetic variant of HIF-1 that did not require free radicals to be stable. In these cells, antioxidants no longer had any cancer-fighting power.
The research was funded by the National Institutes of Health. Authors on the paper are Dean Felsher of Stanford; and Gao, Huafeng Zhang, Ramani Dinavahi, Feng Li, Yan Xiang, Venu Raman, Zaver Bhujwalla, Linzhao Cheng, Jonathan Pevsner, Linda Lee, Gregg Semenza and Dang of Johns Hopkins.
The second publication is a review published in late September in Seminars in Preventive and Alternative Medicine that shows vitamin C may help protect against a range of health disorders, including immune system deficiencies, cardiovascular disease, prenatal health problems, eye disease and cancer (2). The article, titled “Vitamin C Dietary Supplements: An Objective Review of the Clinical Evidence, Part I,” examines data from clinical trials over the past several decades to reveal the growing evidence of vitamin C’s benefits.
The research review, conducted by lead author Mark A. Moyad, M.D., M.P.H., of University of Michigan, examined over 100 studies in more than 10 different medical specialties that evaluated vitamin C as both a standalone supplement and as a nutrient used to enhance combination products. Emerging from the analysis is evidence that suggests vitamin C by itself may provide a significant amount of the health benefits attributed to the combination products.
The third publication was a review by the Orthomolecular Institute regarding research with vitamin C, the common cold and the flu. The Orthomolecular Institute noted that a recent and well-publicized review of vitamin C by the Cochrane Collaboration has resulted in much misguided discussion in the popular press (3).
Several important facts emerge from the review. At least 30 controlled clinical trials (many double-blind and placebo-controlled) involving a total of over 11,000 participants have been conducted. Vitamin C in doses ranging from 200 mg/day to 2,000 mg/day (the dosage range used in a large majority of the studies) reduces the duration of colds by 7% for adults and 15% for children. The data indicate that there is a normal dose-response relationship. Vitamin C is more effective the higher the dose. The most effective doses are far more than 2,000 mg/day. The exclusion of higher-dose studies because they were not placebo controlled is not justified.
The results of a trial conducted in Japan have just been published (4). It is a double-blind, five-year randomized controlled trial involving 439 participants. The supplemented groups received either 50 mg/day or 500 mg/day of vitamin C. The study indicates that vitamin C supplementation does indeed reduce the frequency of colds. The probability of suffering from 3 colds over the course of the study period was reduced by 66% in the group supplementing at 500 mg/day.
For decades, numerous reports from physicians have provided ample clinical confirmation about the effectiveness of vitamin C for treating the common cold (5–7). Orthomolecular physicians have worked with their patients to optimize the dose and have confirmed the conclusions reached by the authors of the Cochrane report that higher doses of vitamin C are more effective (8). They have concluded that patients will benefit by taking as much vitamin C as they can tolerate, and encourage patients to balance the benefits of fighting off a cold sooner with the drawback of intestinal discomforts. These discomforts are harmless and last for a few hours at most. Epidemiological studies associate long-term vitamin C supplementation with health benefits and increased longevity. A 23-year review of collected U.S. poison control center annual reports (9) tells a remarkable and largely ignored story: vitamin C is extraordinarily safe.
Linus Pauling defined orthomolecular medicine as “the treatment of disease by the provision of the optimum molecular environment, especially the optimum concentrations of substances normally present in the human body.” Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information, visit www.orthomolecular.org.
Figure 1: Dr. Linus Pauling and Dr. Richard Passwater, 1973.
Figure 2: Dr. Linus Pauling and Dr. Richard Passwater during a 1976 radio broadcast with a presidential candidate.
Now, let’s turn to Dr. Hickey for an update on the science of vitamin C, the RDA and cancer. Dr. Hickey, after studying mathematics and science at the Open University and pharmacology at Manchester Metropolitan University, earned his Ph.D. in medical biophysics from the University of Manchester. Currently, he is lecturing in decision science and researching biocomputing at the University of Staffordshire, England.
Dr. Steve Hickey, Ph.D., lecturer in decision science and researching biocomputing at the University of Staffordshire, England.
Passwater: Dr. Hickey, what drew your interests to medical biophysics and what is medical biophysics?
Hickey: I was completing my studies in pharmacology when I noticed an advertisement for a Ph.D. studentship in medical biophysics at the University of Manchester, UK. Biophysics is the application of physics to biology, and medical biophysics is its use in medicine. I originally started a degree in mathematics with the Open University, but after taking some biological courses my interest in biology took over.
Biophysics seemed to be an ideal area for a Ph.D. At that time, most members of the department were physicists or chemists, and I was the only biologist. My research was into the structure and function of the spine’s intervertebral disk. I developed a simple mathematical model for the disk and studied its development and aging using x-ray diffraction and electron microscopy.
Passwater: What attracted your interest to vitamin C?
Hickey: I was aware of claims by Drs. Wilfred and Evan Shute and others for vitamin E, and was fascinated when Dr. Linus Pauling published his book, Vitamin C and the Common Cold. Dr. Pauling was the world’s leading chemist and was one of the scientists I most admired.
The principal thing a person can do to avoid disease is to eat healthily. Dr. Pauling explained the importance of vitamin C for maintaining health; other nutrients are also vital, but humans have a specific vitamin C deficit.
Dr. Pauling reported the work of other scientists and physicians, including Dr. Fred Klenner and Irwin Stone. However, Dr. Pauling’s involvement publicized this research along with the problems of conventional medicine.
Passwater: What is the goal of your book, Ascorbate: The Science of Vitamin C?
Hickey: Following Dr. Linus Pauling’s death, Dr. Hilary Roberts and I were concerned that misinformation about vitamin C had increased and had not been challenged properly. At that time, it was generally accepted that the National Institutes of Health (NIH) had shown that the body did not absorb doses of vitamin C above about 200 mg. It was clear that there was a contradiction between this and claims for high-dose vitamin C. If only low doses are absorbed, then the claims must be false.
The NIH published their research shortly after Dr. Pauling’s death and met with little critical response. Although few nutritionists believed the NIH results, there was apparently no reason to doubt their validity. If the NIH were correct, however, Dr. Pauling and the orthomolecular physicians had been misled and high-dose vitamin C would be useless.
Around the 10th anniversary of Dr. Pauling’s death, we decided to review the current evidence on the benefits of vitamin C. Our aim was to bring more rationality into a subject characterized by prejudice and lack of objectivity. In particular, we wanted to explain the discrepancy between the orthomolecular claims for vitamin C and the experimental work, which apparently indicated it was not absorbed at high doses.
Passwater: Why was it needed?
Hickey: Dr. Pauling did a lot to popularize the claims for high doses of vitamin C in preventing and treating infections, heart disease, and cancer. However, current medical thinking was inconsistent with clinical observations on high-dose vitamin C. Dr. Archie Kalokerinos, in his book Every Second Child, describes using high-dose vitamin C to bring sick children back from the brink of death, within minutes. Dr. Ian Brighthope states that vitamin C could reverse AIDS. Drs. Pauling, Cameron and Hoffer presented data showing that vitamin C prolongs the lives of cancer patients. Multiple independent physicians replicated these effects, which seemed to show that high-dose vitamin C could have astounding results.
If these powerful claims for vitamin C were correct, the NIH claims that the body was saturated at a low dose must be wrong, or vice versa, since the two ideas were incompatible. In science, contradictions and paradoxes indicate areas where we are ignorant of the underlying mechanisms and show where progress can be made. To us, the contradiction was an indication that there was fun to be had, getting to understand the workings of vitamin C in the human body.
Passwater: Why did you bother to take the time and effort to write the book rather than just ignoring the issue?
Hickey: The honest answer is that it would have been easier to ignore the vitamin C issue. So-called “quackbusters” or “skeptics” often attacked scientists working in the area. We have no respect for such negative people; they have no original ideas, but attack people on the fringes of science, who present soft targets. We expected a backlash, though it hasn’t materialized so far.
From the outset, our approach was to challenge anyone peddling invalid science or poor scientific methods. Rather unexpectedly, we found that the conventional medical science was suspect and the orthomolecular claims relied on a sound scientific footing.
We ignored the issue for as long as possible. While we were doing this, people we knew and cared for were becoming unnecessarily sick and dying. It is difficult to suggest to someone dying from cancer that, contrary to what their oncologist has said, they might live for another decade or two. People respect the authority of doctors and find it difficult to act independently. Even in a life and death situation, when the potential benefits are large for little associated cost, people are unwilling to follow what they see as flaky, holistic mumbo-jumbo.
When we pointed out the background information, our sick friends and their families made statements like, “If what you say is right, the hospitals would be using it.” Some were medically trained and could not bring themselves to question the assumptions that had brought them a lifetime of success in the profession.
In the end, we had no choice. If we wrote a book, we could salvage our consciences by providing a copy and not entering an unproductive discussion. We hoped, as Dr. Linus Pauling suggested, that they would see the benefits of thinking for themselves.
Passwater: You have found several flaws in the “official” RDA for vitamin C and other nutrients. You assert that the RDA and the Codex justification for low intakes of vitamin C are both invalid and indefensible. Please elaborate for our readers.
Hickey: It quickly became apparent that the NIH’s work on vitamin C pharmacokinetics did not show that the body was saturated at 200 mg or so. Indeed, their own data indicated that a healthy person could consume at least 18,000–20,000 mg/day and get a corresponding increase in blood plasma levels. We tried explaining this to the NIH researchers, but they did not seem to understand. They refused to collaborate on a paper to amend the claim.
The NIH publications misinterpret their data. Their results showed clearly that the blood plasma was not “saturated,” as they suggested. It seemed to me that they were so keen on showing Dr. Linus Pauling to be wrong that they were unable to see what their data implied.
Vitamin C is unusual in that, at low intakes, it has a half-life of 8–40 days. The kidneys actively prevent it from being excreted. When vitamin C is in short supply, this is an essential mechanism for animals such as humans that do not synthesize the vitamin internally. At high doses, however, the half-life is only about 30 minutes. Given this fast excretion time, the NIH had waited too long to measure the blood levels. By the time they took their measurements, the vitamin C dose had been excreted, so the plasma level did not increase greatly with the dose. Instead of realizing that a once or twice daily dose interval was too long, they thought the body had become saturated.
We gave the NIH a year to consider the need for a correction or to support their saturation statements. When they did not respond, we published our Ascorbate book.
Passwater: You have contacted various “official agencies” about the RDA problem. Have you gotten any action or feedback?
Hickey: The U.S. Institute of Medicine used the NIH experiments to justify an RDA of less than 100 mg/day. When we explained to the RDA committee that their recommendations relied on faulty evidence, they referred us back to the NIH. The NIH refused to provide a defense of their claims.
Strangely, we were asked to direct any subsequent questions to the office of the director of the NIH. We presumed this meant our objections might have political implications. We were just interested in the science, but some people suggested that the government could be embarrassed if people realized that they had made such fundamental errors in recommendations for vitamin C. If the government experts could be so wrong with vitamin C, why should we believe any recommendations they make on nutrition?
We were disappointed that the U.S. Institutes of Medicine, the NIH and UK government organizations simply would not explain or discuss their errors. It seemed to us that they thought themselves so important that they could ignore the scientific method. As a result, we amused ourselves writing a short book, Ridiculous Dietary Allowance. This RDA book aimed to demolish the scientific basis of the RDA for vitamin C and, by implication, for other nutrients.
Before publication, we submitted the book to the NIH and Institutes of Medicine, for comments. With consistent form, they declined our offer.
Passwater: You mention in Ridiculous Dietary Allowances that the recommended dietary intake for vitamin C owes more to politics and prejudice than to science. Furthermore, the research behind the RDA values for vitamin C is biased and insubstantial.
Hickey: When we looked at the published justification for vitamin C’s RDA, we could find no evidence to support the recommendations. The Institute of Medicine had ignored data on high doses. They had failed to realize that vitamin C has a short half-life and had taken the NIH data at face value. One of the most worrying aspects was their willingness to introduce arbitrary “fudge factors.” We gained the impression that they had decided what levels they were going to recommend and tried to find data to support their prejudice.
A similar situation exists with the other vitamins and minerals. The RDA committee assumes vitamin E is a single substance and uses d-alpha-tocopherol to estimate requirements. However, vitamin E is not a single substance but is defined physiologically by a deficiency of fat-soluble antioxidants in the body. Many molecules provide vitamin E activity and each one is pharmacologically different. At least four naturally occurring tocopherols and four tocotrienols may be described as vitamin E. Synthetic tocopherols and tocotrienols add many more vitamin E molecules. Even the chemically unrelated substance, alpha-lipoic acid, has vitamin E activity.
The RDA committee explicitly excluded this array of molecules, each of which has its own properties. By making recommendations for “vitamin E” based on alpha-tocopherol, they uphold the myth that these different nutrients are nutritionally identical. Most papers on “vitamin E” are misleading for this reason. We may be told that “vitamin E” does not prevent, say, heart disease. However, what the paper actually indicates is that one form of synthetic tocopherol did not prevent the disease. We are not told that there are many other forms of this vitamin, which might prevent heart disease. Many claims that vitamin supplements are ineffective are based on a prejudiced interpretation of the data.
It appears that current nutritional “authorities” assume that medical politics requires them to recommend only low doses. They seem to be engaged in a form of groupthink, constrained to ignore the data and follow the perceived conformist position. This inherent bias is predictable in a group that is pre-selected for its opinions in nutrition. By selecting the RDA committee, these organizations can get any recommendation they wish. I am sure you could easily pick a dozen doctors who would suggest RDA levels of vitamin C. In the same way, you could select a different group, who would recommend an optimal intake of 10 grams or more.
Passwater: Didn’t you uncover a bias in the Medline compilation of research reports about nutrients?
Hickey: The problem with Medline is one of selection bias again. Medline appoints a committee to judge which journals should be indexed. If your journal is not indexed, it can be overlooked, since Medline is a primary source for medical research.
Researchers want people to notice their work and tend to publish in the journals with the highest impact. Many researchers will avoid publishing in a journal that is not indexed in Medline. Thus, excluding a journal from Medline is a powerful way of censoring medical science.
The problem arises because the Medline committee is chosen from a narrow group of conservative physicians and scientists who support the status quo. For example, there has never been a committee member with a background in orthomolecular or nutritional medicine. So, the committee can arbitrarily exclude any journal that covers subjects that conflict with the current medical or political paradigm.
The evidence is clear. The Reader’s Digest and the Times newspaper are included in Medline. Presumably, they are considered to contain articles of scientific merit. However, the American Journal of Physicians and Surgeons, the Journal of Nutritional and Environmental Medicine and the Journal of Orthomolecular Medicine are excluded. Physicians are expected to refer to articles in The Reader’s Digest for medical information, while the American Journal of Physicians and Surgeons is kept from them.
Passwater: Are most scientists looking at the wrong model of vitamin C action?
Hickey: The current idea of vitamin C as a micronutrient assumes that it is required in small amounts in humans. Oddly, we are given no reasons why humans should be different from the other mammals or primates, who either synthesize vitamin C internally in large amounts or require a gram level intake.
Vitamin C acts typically as an antioxidant, an electron donor. Many of its actions depend on this process. When vitamin C is absent from the diet, a person will get sick and die from acute scurvy within a few months. The conventional assumption is that if you have enough vitamin C to prevent acute scurvy, you have all you need.
However, there is no evidence to support the contention that the few milligrams needed to prevent acute scurvy are optimal. One reason is that it is extremely difficult to get solid evidence on the effect of nutrients on long-term, chronic disease. Vitamin C has some properties that make it particularly difficult to study. Indeed, since the half-life of vitamin C is so short, nearly all the high-dose studies are invalid. Typically, studies have used a single- or twice-daily gram level dose of vitamin C. These doses have a limited effect on minimum or median blood plasma levels, as the dose is excreted rapidly. This is the same error as the NIH made in recommending their RDA, and it pervades the last 50 years of medical studies of high doses of vitamin C.
Some scientists are trying hard to show that high doses of vitamin C are damaging to the body. Their idea is that vitamin C at high doses will act as an oxidant, rather than an antioxidant, when some chemicals and metals (like iron or copper) are present. They believe that too much vitamin C can cause free radical damage. However, this aspect of the action of vitamin C provides one of its greatest health benefits: its ability to kill cancer cells.
Passwater: We’ll come back to that important point later. But first, let’s continue with what is incorrect and correct for scientists to look at regarding vitamin C. What should they be looking at?
Hickey: Dr. Robert Cathcart pointed out that vitamin C is a unique antioxidant, since it can be taken in massive doses (more than 100 grams per day) without harm. He also observed that bowel tolerance increases when a person is sick. A previously healthy subject, who could only take a couple of grams without getting loose bowels, might manage as much as 150 grams if they have a disease such as the common cold. Cathcart described a mechanism whereby vitamin C molecules in a sufficiently high dose can quench free radicals and inflammation, removing the symptoms of infectious and allergic diseases.
Taking account of the short half-life of high doses of vitamin C, we have a mechanism for the rapid removal of the absorbed dose. During infectious disease, massive doses of vitamin C flood the system. Each vitamin C molecule can donate two antioxidant electrons before it is excreted. Damaged and sick cells no longer have to manufacture antioxidants to fight the damage caused by the disease; the flow of vitamin C takes their place. This is the basis of our new model of vitamin C, which we call dynamic flow.
Another factor is at work. Under some conditions, vitamin C acts as a free radical generator. Fortunately, those conditions occur inside tumors and virally infected cells. Cancer cells contain free iron and copper, and have faulty antioxidant defenses. Together with iron or copper, high levels of vitamin C generate hydrogen peroxide, which attacks cancer and virally infected cells. In healthy cells, these metals are bound to protein and so vitamin C does not produce hydrogen peroxide. Also, any hydrogen peroxide that might be produced is rapidly deactivated by cellular enzymes, such as catalase and peroxidase. Cancer cells are deficient in such enzymes, so they cannot destroy the hydrogen peroxide, which kills the cancer.
Understanding the action of vitamin C in cancer cells has allowed us to recognize cancer as a redox disease. We can think of carcinogenesis as a disturbance in the oxidant/antioxidant balance in the cell. This balance is a primary control mechanism for cell growth, cell division and cell death by apoptosis. Observations on vitamin C led us to a new model of cancer based on the microevolution of cells with a faulty antioxidant/oxidant balance.
Passwater: Ever since Dr. Albert Szent-Gyorgyi discovered vitamin C and the bioflavonoids, there seems to have been a misunderstanding and controversy over their role, especially from the American scientists. What is their problem?
Hickey: The problems seem to have originated with the definition of a vitamin as a micronutrient, required in small amounts in the diet. A vitamin or “vital amine” was defined as something required in the diet, which prevents an acute deficiency disease. In the case of vitamin C, the disease was scurvy, and it was clear that a person needs only a few milligrams to prevent it.
The micronutrient definition of a vitamin constrained early considerations of the human requirement for vitamin C. There was no drive to determine the optimal intake of vitamin C. It was assumed, without evidence, that if there was enough in the diet to prevent acute scurvy, no more was needed. Looking back, this seems to indicate a complete failure of the scientific method in nutrition. In defense of the early work, however, it might not have been clear how to determine the optimal intake to prevent chronic disease. The problem of studying the long-term effects of sub-acute deficiency is still with us.
There is increasing research interest in the actions of high doses of vitamin C, particularly in cancer. Much of this research is coming from countries other than the United States and the United Kingdom, such as Mexico, Korea and Japan. The lead in this research may be switching away from the developed Western nations. However, this could change as people begin to realize the potential.
A notable researcher was the late Dr. Hugh Riordan, who demonstrated the likely value of massive doses of vitamin C and lipoic acid in combating cancer. The NIH have since replicated this work and gained publicity for their efforts, but as far as I can see, they have merely repeated work by Dr. Riordan. If we are not careful in the coming decades, the original work of Drs. Riordan, Pauling, Cameron and Hoffer could be downplayed, as conventional medicine rewrites history.
Passwater: We’ll be following up with Dr. Riordan’s work later with a chat with Dr. Ron Huninghake. We will also be looking at ways to improve vitamin C uptake from supplements and the use of intravenous vitamin C when needed. Does the evidence show that improving vitamin C intake will reduce disease?
Hickey: The available evidence is consistent with high doses of vitamin C greatly reducing the incidence of disease. Given in sufficiently high doses, it may also provide a powerful treatment. Clinical reports of the benefits of high doses of vitamin C have been made for over half a century. Mostly, these reports have been assumed to be false in some way, although critics have provided no evidence for this assumption. The medical establishment has not carried out the research needed to evaluate the claims, one way or the other.
Suppose, for example, that vitamin C at repeated high doses completely prevents coronary heart disease. This may be the case, as there is insufficient clinical evidence to refute the proposal. One reason for the lack of evidence might be that studies to show that high doses of vitamin C would prevent heart disease would take years to carry out. Furthermore, when studies have been undertaken, they have been constrained by the idea of vitamin C as a micronutrient. So, the researchers consider 200–1000 mg per day as a high dose, whereas the strong claims for vitamin C are in the range of 10,000 mg per day, or above. Despite heart disease being the biggest killer in the industrial world, there is limited evidence on the role of vitamin C. The clinical evidence that is available at these high doses suggests that vitamin C can prevent atherosclerosis and heart disease, and can partly reverse the clinical disease.
Passwater: Which diseases and how important is vitamin C in reducing the risks of these diseases?
Hickey: In sufficiently high doses, vitamin C is claimed to prevent and treat most viral diseases, from the common cold to polio and AIDS. The claimed effects equal or exceed the actions of antibiotics in bacterial infections. This would seem to warrant a great deal of scientific interest, since few antiviral agents are available and those that exist are relatively ineffective and toxic. However, few conventional physicians or scientists have investigated these properties. Once again, they are assumed to be wrong, without any evidence to the contrary.
I was recently asked to respond to an update of the Cochrane review of vitamin C and the common cold. It had undergone a minor revision and the media was flooded with reports that vitamin C was ineffective against the common cold. However, this same review included two responses, indicating that its conclusions were invalid. The first response was by Dr. Julian Higgins, who reported that the doses studied were too small for either prevention or treatment. The second response, from Dr. Hilary Roberts and me, pointed out that the doses were at least 10 times too small to be effective and the researchers had ignored the short half-life of vitamin C. The Cochrane authors did not address these issues in their published reply. However, the media did not notice that the Cochrane review had included published responses invalidating its conclusions.
Critically, the actions of vitamin C against cancer are becoming clear. As evidence accumulates, we can see that the claims of Dr. Linus Pauling and others may even have understated the vitamin’s potential for the prevention and treatment of cancer. Within tumors, massive doses of vitamin C provide a driving force for substances such as iron, copper and lipoic acid to generate hydrogen peroxide. Thus, it is possible to kill or slow the growth of cancer, while leaving normal cells unharmed.
Vitamin C alone is a relatively weak anticancer agent, but it is synergistic with other anticancer nutrients. There is a myth that non-toxic anticancer agents are difficult to find. According to this, pharmaceutical companies have been engaged on a prolonged and extensive search for anticancer agents. Surprisingly, such agents are easy to find and common in foods; an example is curcumin in the spice, turmeric. As Dr. Hilary Roberts and I pointed out in our book, Cancer: Nutrition and Survival, a quick search of the Medline database turns up numerous such nutrients. The difficulty is that such substances are not patentable, so drug companies cannot make large profits from them. This is not a conspiracy, however; the principal aim of a pharmaceutical company is to make profits for its shareholders. The problem may be that governments and the medical establishment have allowed drug companies to take the lead in this area.
Passwater: What should be the RDA for vitamin C and what would be an optimal intake for optimal health?
Hickey: A basic principle of orthomolecular medicine is individual variability. Since everyone is biologically unique, the idea that a single, general, daily intake of a nutrient can be determined for all is inappropriate. This is particularly the case with vitamin C. Vitamin C requirements can vary by two orders of magnitude (or 100 fold) between individuals. Furthermore, one person’s daily need may also vary 100 fold from one time to another, depending on his or her state of health.
Dr. Robert Cathcart showed that the bowel tolerance level, the maximum amount a person can consume without getting loose stools, varies among individuals and according to a person’s health. This is a mechanism to allow the body to absorb greater amounts of vitamin C when it needs more. We might suggest a healthy intake of greater than 50% of bowel tolerance, in divided doses, throughout the day. This would mean a minimum of, perhaps, 2.5 grams each day. However, sick people are advised to take 90% or more of their bowel tolerance, which, as Dr. Cathcart has suggested, may be curative in many conditions.
Conventional medicine has steadfastly refused to address these intakes in research, nutrition or therapy. There appears to be a feeling that the intakes are so abnormal that taking them seriously could be damaging to a scientist’s reputation or even a doctor’s license to practice. However, to assume that the evidence can be ignored because you “know” the answer is one of the critical failings of medicine throughout history.
Passwater: What will be your next effort to correct these problems that you have uncovered?
Hickey: We are currently expanding our model of cancer as microevolution. A core feature of the microevolutionary model is that the cell’s redox balance (the relative levels of antioxidants and oxidants) controls its division, behavior and death. We are increasingly finding that antioxidants and vitamin C are critical elements in cancer, viral infections and chronic disease, and that there is a solid basis for this in biology and cellular cybernetics. We also are interested in Dr. Abram Hoffer’s work on nutrients and mental disease, particularly niacin, omega-3 oils and vitamin C. Schizophrenia may yet turn out to be a redox disease.
Passwater: Thank you, Dr. Hickey, for updating our readers on the value of vitamin C in optimal health. WF
SIDEBAR: Pauling Once Again Validated
I am so pleased to see so many researchers remembering the teachings of Dr. Linus Pauling. I have not been able to write about Dr. Pauling since his death in 1994 at the age of 93. One of these days, I may find the emotional strength to write a tribute to him. Dr. Pauling was a genius and my hero. He was the premier chemist of the 20th century and a founder of molecular biology and orthomolecular medicine. I had the opportunity to research, publish and lecture with Dr. Pauling on several occasions. I also had the opportunity to work with Dr. Pauling on political peaceful purposes, but that is another story for another day.
Dr. Pauling was kind enough to write a special note on the cover of my first book for the general audiences. On the front cover of Supernutrition: Megavitamin Revolution (1975), Dr. Pauling wrote, “Supernutrition is an important book, for it brings to attention many facts about nutrition that are not generally known and, for the most part, not accepted by physicians and nutritional authorities. I am sure that health can be improved significantly by the proper amounts of vitamins and nutrients—and by a decrease in the consumption of sugar and some other substances. Reliable information about these matters is presented in Supernutrition.”
One of my proudest moments was when Dr. Pauling told People magazine five years later that “Passwater is reliable with a good background and knowledgeable” (December 15, 1980). Figure 1 is a photo of Dr. Pauling and me from 1973. Figure 2 is from 1976 when we were doing a radio broadcast with a presidential candidate and discussing how science can advance peace in the world.
We conferred frequently via telephone and also corresponded via letters. I have a file drawer full of letters that cover our journeys through research and peace efforts. I miss this stimulating dialog! In a letter dated October 21, 1983, he said, “As you know, I recommend your books to everyone.” On May 20, 1992, he wrote, “I think about you often and remember our association over the years.”
Dr. Pauling and I wrote a joint letter in 1976 to all of the California participants of my 1974 study on vitamin E. We expanded the study to include all vitamins. This study was joined by epidemiologist Dr. Jim Enstrom of UCLA and published in the Proceedings of the National Academy of Sciences in 1982 (10). It concluded, “During 6 years of follow-up, a total of 107 deaths occurred. Based on comparison with 1977 United States whites, the standardized mortality ratio (SMR) is 78% for the males, 54% for the females, and 68% for both sexes combined. All three SMR values are significantly less than 100% (P less than 0.05). For both sexes combined, the SMR is 86% for cancer, 62% for total cardiovascular diseases, and 73% for all other causes. Only the cardiovascular SMR is significantly lower than 100%. The death rate for the males is approximately the same as that reported among other healthy nonsmoking questionnaire respondents, but the death rate for females is significantly less (P less than 0.01). The only notable relationships between questions asked in 1974 and subsequent mortality are those indicating a higher mortality rate associated with inactivity, heart trouble, and very low and very high levels of vitamin E intake. For this highly selected cohort, the overall ‘Prevention life-style’ appears to be a healthy one.”
It is fairly widely known that Dr. Pauling received two Nobel Prizes. However, few people realize the significance of the importance of the research and effort that resulted in the awards. The first Nobel Prize awarded to Dr. Pauling was the Nobel Prize for Chemistry in 1954. This award was for his discoveries of the nature of chemical bonds, which helped the research of every chemist and biochemist since. He also pioneered the application of quantum mechanics to chemistry (which gave me fits in calculations in graduate inorganic chemistry courses). He also made important contributions to determining the structures of proteins. In addition, Dr. Pauling came near to elucidating the structure of DNA. Dr. Pauling had discovered the alpha-helix nature of DNA, but had not figured out all of the inter-relationships. Drs. James Watson and Francis Crick, having access to high-quality x-ray diffraction photographs of DNA, beat him to it in 1953.
The second Nobel Prize given to Dr. Pauling was the 1962 Peace Prize. This award was for his efforts to save many thousands of Americans and other people from needless cancer and death due to airborne radiation. Dr. Pauling understood the importance of the United States having a nuclear deterrent to discourage attacks against us. However, countries were exploding nuclear bombs on the Earth’s surface as if they had no detrimental long-term health effects as the radiation clouds drifted around the planet. Dr. Pauling secured the signatures of 11,000 scientists on a petition to stop the airborne testing of nuclear weapons.
Later, Dr. Pauling and I tried to do our part in encouraging a reduction in the over-kill in armament and wasted resources. On August 25, 1989, just before the collapse of the Soviet Union, Dr. Pauling wrote to the USSR Ambassador to the United States, Yuri Dubinin, to arrange a meeting. Dr. Pauling began with “An old friend of mine, Richard Passwater, [is helping my efforts to] achieve continued world peace and to move toward disarmament and decrease in the military budgets of the great nations.” The meeting was held and doors were further opened between our nations. Dr. Pauling valued his Nobel Peace Prize over his Nobel Prize for Chemistry.
Well, that’s enough of sharing old memories. Linus, you and your work are not forgotten. The world will continue to learn from your teachings.
1. P. Gao, et al., “HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo,” Cancer Cell 22, 230–238 (2007).
2. M.A. Moyad, “Vitamin C Dietary Supplements: An Objective Review of the Clinical Evidence, Part I,” Seminars Prevent. Alt. Med. 3 (1), 25–35 (2007).
3. R.M. Douglas, et al., “Vitamin C for Preventing and Treating the Common Cold,” Cochrane Database Syst. Rev., Issue 3, CD000980 (2007).
4. S. Sasazuki, et al., “Effect of Vitamin C on Common Cold: Randomized Controlled Trial,” Eur. J. Clin. Nutr. 60 (1), 9–17 (2006).
5. R.F. Cathcart, “Vitamin C, Titrating to Bowel Tolerance, Asascorbemia and Acute Induced Scurvy,” Med. Hypotheses, 7 (11), 1359–1376 (1981).
6. F.R. Klenner, “Significance of High Daily Intake of Ascorbic Acid in Preventive Medicine.” Megascorbic Therapies: Vitamin C in Medicine. Volume 1, Issue1, www.vitamincfoundation.org/news.htm. See also: A.W. Saul, “Hidden in Pain Sight: The Pioneering Work of Frederick Robert Klenner, M.D.,” J. Orthomolecular Med., 22 (1), 31–38 (2007).
7. L.H. Smith and F.R. Klenner, “Clinical Guide to the Use of Vitamin C,” www.seanet.com/~alexs/ascorbate/198x/smith-lh-clinical_guide_1988.htm.
8. T.E. Levy, Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins (LivOn Books, 2002).
10. J.E. Enstrom and L. Pauling, “Mortality Among Health-Conscious Elderly Californians,” Proc. Natl. Acad. Sci. U.S.A. 79 (19), 6023–6027 (1982).
© 2007 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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