Linus Pauling (1981) - Vitamin C in the Prevention and Treatment of Cancer

I am going to speak about vitamin C and cancer. I hadn't planned to work on cancer, work that I began, in fact, 10 years ago, nor to work on vitamin C or other vitamins as I began around 16 years ago. Instead I got into these fields by accident, or through some concatenation of circumstances that just left me, led me into these fields. I started to work on haemoglobin after having worked on simpler molecules for 14 years in 1936, and then the next year I began some work, together with my students of course, in the field of immunology. Then in 1945, I had an idea that sickle-cell anaemia might be a disease of a molecule, rather than a disease of a cell. Dr. Harvey Itano, a young physician, came to study with me and he and I began to check up on this idea. In 1949, together with two other students, Singer and Wells, we published a paper; "Sickle-Cell Anaemia, a Molecular Disease". After being with me 8 years, Dr. Itano was ordered as an officer of the public health service to move to Bethesda. And I decided that I should give up work on the hereditary haemolytic anaemias. It didn't seem to me very sensible of me to be competing with such an able and vigorous young investigator as Dr. Itano. So I thought, why shouldn't I look at other diseases to see whether or not they are molecular diseases? And they might as well be important diseases, because nobody else was working in the field, except by that time there were a good number of haematologists studying the haemoglobin anaemias. I thought, well, I might work on cancer. Or I might work on mental disease. And I rejected cancer for two reasons; one, it seemed to me that it was just too complicated a field for me to be involved in. And second, many people, many investigators were carrying on studies in the field of cancer, whereas in 1954 very few people were working on mental disease. It was of mental disease, our study is on schizophrenia and mental retardation that got me into vitamins. After about 10 years of work in this field I ran across some papers, publications, by doctors Hoffer and Osmond in Canada, Saskatoon, Saskatchewan, Canada. They made a report that really astonished me. They said that they were giving large doses of nicotinic acid or nicotinamide to schizophrenic patients. I knew, of course, that a little bit of nicotinic acid or nicotinamide must be ingested day after day, 5 milligrams, perhaps a little pinch, to keep a person from dying of pellagra. So I knew that these substances, the pellagra-preventing factor, are very powerful substances. And yet these substances are so lacking in toxicity that Hoffer and Osmond were giving a thousand or ten thousand times this physiologically effective amount, or pharmacologically effective therapeutic amount, to schizophrenic patients. Nobody knows just how toxic they are, people have taken 100 grams a day, or even more, without any serious side effects. I thought, how astonishing that there are substances of this sort that have physiological activity over a tremendous range of concentration, 1,000 fold or 10,000 fold range of concentration. In fact I found that Milner had been giving large doses of vitamin C in a double-blind experiment to schizophrenic patients and he reported that several grams, perhaps the thousand times the amount that will prevent scurvy in most people, several grams of ascorbic acid is also effective, more effective than a placebo, for these schizophrenic patients. The idea, that such substances exist, which are effective in one way or another over a tremendous range of concentrations, caused me to decide that this field of medicine deserved a name. I invented the word 'orthomolecular' to describe it. The right molecules are the molecules that are normally present in the human body, and the right amounts are they amounts that put people in the best of health. Well, I was interested in infectious diseases in relation to vitamin C originally, but in 1971 Charles Huggins asked me to speak at the dedication of his new cancer research laboratory. I thought, I must say something about cancer. So I remembered that I had read a book published in 1966 by Ewan Cameron, a surgeon in a hospital in Scotland who had been a general surgeon who had however all of his life as a surgeon been interested in cancer. He formulated a general argument in this book, "Hyaluronidase and Cancer". His argument was this - he said "the body has protective mechanisms, the immune system for example. If we could potentiate these, the natural protective mechanisms, they might provide additional protection against cancer". As Professor de Duve pointed out, we have, in many patients, most patients with cancer, circulating cells, but not all of them develop metastases. Those, whose immune systems are functioning well, have a smaller chance of developing metastatic cancer than those whose immune systems are not functioning well. Well, I thought, we know one thing about vitamin C, it is required for the synthesis of collagen. If then, persons with cancer were to be given larger amounts of vitamin C, they would be stimulated to produce more collagen fibrils in the intercellular cement that holds the cells in normal tissues together. These tissues might become strengthened in this way to such an extent that, as Cameron pointed out, without mention of vitamin C, to such an extent that they could resist infiltration by the growing malignant tumour. Dr. Cameron saw a newspaper account of my talk and wrote asking how much vitamin C to give. I replied he should give the patients 10 grams a day, 10,000 milligrams, 200 times the usually recommended amount. He began, cautiously, with one patient in Vale of Leven Hospital, Loch Lomond side, Scotland, and was astonished by the response of that patient, to such an extent that he gave 10 grams of vitamin C a day to a second terminal cancer patient, an untreatable patient receiving no treatment other than the vitamin C and narcotics to control pain. And then a third and fourth and more and more patients as he became more and more convinced of the value of this substance for patients with cancer. I, me, have started out now with the first slide. Well, I think, and perhaps this is the message that I should emphasise, I think that the people in the field of nutrition, the scientists in the field of nutrition, which up to 15 years ago seemed to me to be a terribly boring subject, have been off on the wrong track. They have said that a vitamin is needed, it's an organic compound needed in small amount to prevent death by a corresponding deficiency disease. And they have striven, very vigorously, over a period of 40 or 50 years, to find out just how much each of these substances is needed to keep people from dying. I believe that the problem that should be attacked is that of finding the intake that would put people in the best of health, not just the amount that will keep them from dying. The nutritionists refer to their recommend dietary allowances, RDA, by saying that these are the amounts that will prevent most people from developing the corresponding deficiency disease. Most people in ordinary good health. What they should say is that, it will prevent most people who are in what is ordinary poor health from dying from the corresponding deficiency disease. To be in what ought to be ordinary good health, they need to be ingesting the optimum amounts, the proper amounts, of these valuable substances. Next slide. There's an interesting difference between vitamin C and the other vitamins. The other vitamins, thiamine, pyridoxine, riboflavin, vitamin A and so on, are required by essentially all animal species. Vitamin C is not required by most animal species, 99% or more of animal species synthesize ascorbate, they do not rely on the dietary sources of the substance. If I ask, why do these animals continue to synthesize vitamin C even though they may be getting large amounts by ordinary standards in their diet, several grams a day for an animal the size of a man, the answer surely is that they continue to synthesize ascorbate because the amounts they get in their diet are not enough to put them in the best of health, not enough to put them in the fittest condition in the environments in which we live. Next slide. Man is one of the few unfortunate species of animals who are in rather poor health generally because of not having as much ascorbate as corresponds to the best of health. When I looked at 150 raw natural plant foods, taking the amounts that would give 2,500 kilocalories of energy, I found that for thiamine and other vitamins there was perhaps 3 times or 5 times as much of the vitamin as is now recommended, as you get in modern diet on the average, but 50 times as much vitamin C as is recommended. And I thought, this is an indication that larger amounts of vitamin C are needed because animals are getting these larger amounts but continue to make ascorbate. Next slide. The next slide please. Another interesting fact is that the committee that recommends the diet, the food for monkeys, experimental monkeys, recommends 70 times as much vitamin C. Monkeys also require exogenous vitamin C, they are primates and all of the primates require this vitamin. I think that this is understandable, monkeys are very valuable, experimental monkeys, if you've spent months carrying out studies with them and then suddenly your monkeys die, it's a real tragedy, so that a great effort has been made to find out how much vitamin C will put the monkeys in the best of health. No one has gone to the effort to carry out corresponding studies for human beings. Next slide. Well, I mentioned that these most species of animals synthesize ascorbate. The amount they synthesize depends on the size of the animal; small animals produce a small amount, large ones a large amount. Proportional to body weight, not to surface area, 2/3s however of the body weight, but to body weight. And the amount produced by different animal species is between 40 and 400 times the usual recommended intake for human beings. Averages 10 grams per day, per 70 kilogram body weight, that's why I wrote to Ewan Cameron, to say that 10 grams a day is the amount that he should try. I might say that the pharmacologists sometimes say that 50 milligrams a day of vitamin C per day is a physiological intake and that 10 grams a day is a pharmacological intake, that the vitamin is being used as a drug. I would say that 10 grams a day is the proper physiological intake and 100 grams a day might be called the pharmacological intake. And people have taken that amount, people have received 125, 150 grams of sodium ascorbate a day by intravenous infusion to control serious diseases, without any side effects, and have taken similar amounts by mouth. Next slide. So, this is the conclusion that I have reached. I have already stated it. Next slide please. Well, vitamin C is required for synthesizing collagen and I think it might well strengthen the normal tissues. Next slide. The reason that it is required is that collagen is formed from procollagen by hydroxylation of prolyl and seryl residues and there are other hydroxylation reactions, this one and other similar reactions do not take place except with use of vitamin C. Next slide. Well, collagen, the value of increased intake of vitamin C, under several circumstances, has been known for a long time, and surgeons for over 40 years have been recommended in the better surgical text books to give all surgical patients 1 gram or 2 or 3 grams of vitamin C per day in order to facilitate wound healing, healing of broken bones, of burns, to take care of peptic ulcers, periodontal disease, physicians have known, and dentists too, have known about this, they don't all practice it, but it's been known. Next slide. Here is a reference to Ewan Cameron, my associate for 10 years now in this work, and to his book "Hyaluronidase and Cancer". Next slide. And I argued then, in 1971, stated on this slide, that the increased synthesis of collagen might strengthen normal tissues to a significant extent. Next slide. Since then, a large amount of information has been gathered about the relation between intake of vitamin C and various aspects of the immune protective mechanisms. Vallance, Fagan, Yonemoto, others have shown that antibodies, IgG and IgM are produced in larger amounts with the increased intake of ascorbate. Fagan showed that a component of complement involving collagen-like sequences of amino acids, as shown by Prof. Porter, is produced in larger amounts, the blastogenesis of lymphocytes occurs at a greater rate, the activation of cytotoxic macrophages has been shown to be increased and interferon production is reported to be greater with a greater intake of vitamin C. I might mention that there's been a tremendous amount of interest in interferon for the treatment of cancer. One important point here is that to treat a patient with interferon costs about a thousand times as much as to treat him with ascorbic acid. Dr. Cameron says to people who ask about interferon, take ascorbic acid and synthesize your own interferon. Next slide please. This is the only study on vitamin C that has been carried out in the National Cancer Institute of the United States, Yonemoto, Chretien and Fehniger gave vitamin C, 5 grams a day for three days, to volunteers. The rate of blastogenesis of lymphocytes under antigenic stimulation doubled with this intake. When 10 grams a day for three days was given the rate tripled, and when 18 grams a day for three days was given the rate quadrupled. It's known that a high rate of blastogenesis of lymphocytes in the cancer patient is correlated with a better prognosis, longer survival, than a lower rate of blastogenesis. Next slide. Ascorbate seems to have a significant prophylactic value. Here I have listed seven studies relating to vitamin C and cancer, studies in which when a number of environmental or nutritional factors were correlated with the morbidity from cancer, vitamin C turned out to have the highest correlation coefficient, negative of course, to be the factor that seemed to be most strongly related to morbidity from cancer. Next slide. An interesting study was carried out by Dr. DeCosse and his associates. DeCosse is now the head of surgery in the Memorial Sloan-Kettering Cancer Centre in New York City. He found that 3 grams a day of vitamin C given to patients with familial polyposis caused the polyps to disappear in half of the patients. I've suggested that he give 10 grams a day in a new trial, which is underway, but he is sticking with 3 grams a day because of his worry about toxic side effects of large doses. Well, there just aren't any toxic side effects of large doses of vitamin C, talk about kidney stones has essentially no basis whatever, no cases in the medical literature. Damage to the liver doesn't occur, although it's sometimes mentioned without references. Next slide please. Bruce in Toronto has used the Ames-method of testing for mutagens to study faecal material, the contents of the lower intestinal tract and there are many mutagens that show up, and they, of course, when tested by, with much difficulty, various mutagens for carcinogenic activity have usually been found, When vitamin C is given by mouth to patients, the number of mutagens in the faecal material is much less. This is presumably a mechanism for preventing cancer of the lower gastrointestinal tract. I find, when I take 10 grams a day, which is the amount that I do take, that half of the vitamin C, Presumably then providing protection against this tract and in particular, of course, preventing the formation of nitrosamines, which are a cause of gastric cancer and other cancers, but also destroying other mutagens in the materials in the gastrointestinal tract. Of this 30%, 1.5 grams is eliminated in the urine, and provides protection of the urinary tract on the way out, and the other 3 1/2 grams works throughout the human body. Next slide. Here are some clinical tests, all have been carried out that have been reported as yet, I made a mistake when I wrote the copy for this slide, Cameron's last study involved 300 terminal cancer patients treated with ascorbate, compared with 2,000 matched controls in the same hospital. With these studies, a hundred against a thousand matched controls, there was essential random distribution of patients between Dr. Cameron on the one hand and the other surgeons and physicians in the same hospital on the other. Over a period of time when Cameron was giving the patients with terminal cancer, untreatable cancer, vitamin C, and the other surgeons and the physicians were not, so that we had a sort of randomized allocation of students of patients to the two groups. Morishita and Morata are associates of our institute in California, Morata has worked there two summers and their work is carried out in a hospital in Japan. Next slide. The first thing that Dr. Cameron and his collaborators, the surgeons working with him, noticed was that the patients feel better when they receive ascorbate. Cancer patients usually are pretty miserable, don't feel well, they have poor appetites and don't eat well. These patients lost their cachexia, they began to feel lively, feel well, have good appetites and then there were other responses that were noted. And later on, of course, it was found, next slide, it was found that they survived longer than the controls. This slide shows survival times of the hundred patients with untreatable cancer who received ascorbate, and the thousand matched controls. Ten matched to each of the ascorbate-treated patients who had also reached the untreatable stage when no therapy was administered to them except morphine or diamorphine to control pain. After the date of untreatability, the controls lived on the average 54 days, and the ascorbate treated patients lived on the average about a year, much longer. Of the controls only three in a thousand, 3/10 of 1%, survived over 400 days, 4/10 of 1% over a year after untreatability, whereas around 16% of the ascorbate-treated patients, who continued to survive. And these patients continued to survive for a long time, as much now as 8 years after having been considered to be terminal with an expected survival time of only a couple of months. Next slide. These are results of similar observations made in Fukuoka Torikai Hospital in Japan, Fukuoka Japan. Again, there's a low ascorbate group, receiving less than 5 grams of vitamin C per day, in Cameron's patients in Scotland the low ascorbate group received very little, perhaps 50 milligrams a day, and the high ascorbate group receiving more than 5 grams a day, an average of about 15 grams a day. The curves, the survival curves are essentially the same as for the study in Scotland. These graphs represent a breakdown of that comparison of a hundred, the first hundred ascorbate-treated patients in Scotland, and a thousand matched controls. Here we have seventeen patients with cancer of the colon who had reached the untreatable stage, compared with a 170 matched controls. The controls died off pretty rapidly, the ascorbate-treated patients lived on, a number of them here, With cancer of the stomach, bronchus and breast, the situation is rather similar. Next slide. Cancer of the kidney, rectum, bladder, ovary, there doesn't seem to be much difference in the response of patients with different kinds of primary cancer to ascorbate. There are some statistically significant differences, but it's a difference between living a year longer on the average and living 7 months longer. In general, I would say these patients, who have reached the untreatable stage and in Scotland, the untreatable stage for adult patients with solid tumours, gastrointestinal tumours and so on, do not receive chemotherapy so that these patients in general had not been treated with chemotherapy. In general, I would say that the evidence indicates that to give them ascorbic acid leads to greater survival time as well as better well-being during the period of survival, than treatment with chemotherapy does, the standard sorts of chemotherapy that are used now. Next slide. Another trial carried out was by Creagan, Mertel and others in the Mayo Clinic. The difference between that trial and the trials in Scotland and Japan is that 88% of the patients, We argued, Dr. Cameron and I, before the Mayo clinic trial was begun, that they should not use patients who had had their immune systems badly damaged by courses of chemotherapy, because of our feeling that vitamin C works largely by stimulating production of, by stimulating the immune system. Next slide. Well, our conclusions, with the possible, and I just quote from our book, the last sentences in our book concern vitamin C, in the management of all cancer patients from as early in the illness as possible. Next slide. We believe that this simple method, measure would improve the overall results of cancer treatment quite dramatically, not only by making the patients more resistant to their illness, but also by protecting them against some of the serious and occasionally fatal complications of the cancer treatment itself. We are quite convinced that in the not too distant future, supplemental ascorbate will have an established place in all cancer treatment regimes". Next slide. Now the advantages, it is an orthomolecular substance, every human being has vitamin C in his body, so long as he continues to live, has very low toxicity, no serious side effects, makes a patient feel much better, very low cost, it's compatible with most or all other methods of treatment, the exception being chemotherapy. Of course, I think that chemotherapy should be used with childhood cancer, leukaemia, Hodgkin's disease, possibly together with vitamin C, but my own feeling is that vitamin C for adults with solid tumours is probably preferable to chemotherapy. Well, I can end up by saying that in the United States, the medical profession, as an organized group, has not accepted these ideas. Individual physicians, I would judge have, because we get hundreds of letters and telephone calls from individual physicians who have developed cancer asking for more information. Thank you. Applause.

Linus Pauling (1981)

Vitamin C in the Prevention and Treatment of Cancer

Linus Pauling (1981)

Vitamin C in the Prevention and Treatment of Cancer

Comment

After being awarded the 1954 Nobel Prize in Chemistry "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances", Linus Pauling turned his attention to a range of medical issues, including topics like the mechanisms of general anaesthesia or the molecular mechanisms of sickle cell anaemia, which he both discussed in his 1964 Lindau lecture (LINK). He also briefly worked on mental diseases. This brought him to the vitamins, some of which were evaluated as drug candidates for mental patients. What ensued was some of his probably most controversial work, which culminated in the claim that vitamin C megadoses (around 10 g per day) would be suited to treat cancer and support health in general. Pauling himself took at least 10 g of vitamin C per day for more than 20 years. Aged 93, he died of prostate cancer. Before his death, he claimed that vitamin C had delayed the onset of his disease significantly. In the present lecture, Pauling clearly outlines the rationale that led him to support vitamin C megadoses. He begins by pointing out the importance of vitamin C for collagen biosynthesis (collagen is a structural protein responsible for the integrity of skin, hair, muscles, tendons and other tissues) and hypothesizes that vitamin C could inhibit the metastasis of cancer by generally strengthening tissues due to improved collagen synthesis. His second argument concerns the curious fact that the vast majority of animals are able to biosynthesize vitamin C and are thus not dependent on an intake via food. Humans, primates, bats, guinea pigs are some of the exceptions. Pauling extrapolates that a typical animal weighing 70 kg would produce 10 g of vitamin C per day. This is much more than a human will normally take up via food, hence, according to Pauling, heavy supplementation is necessary. This line of thought is the source of his famous 10 g per day megadosage recommendation. However, to date (2013), it has not been proven that vitamin C megadoses are suited as a cancer therapy and the studies Pauling describes in his talk have been shown to contain systematic flaws. In this context, the remarks made towards the end of the talk are highly problematic. Based on the assumptions that (i) vitamin C helps to fight cancer by stimulating the immune system and that (ii) vitamin C can hence not act if the immune system is suppressed by chemotherapy, Pauling recommends to treat adult cancer patients with vitamin C only and to omit chemotherapy altogether. Luckily, this highly questionable recommendation was never adopted by conventional medicine.The Linus Pauling Institute at the Oregon State University, founded in 1973 by Pauling and colleagues, today distances itself from the claim that vitamin C is effective in cancer therapy and recommends a rather low daily intake of 400 mg based on the “currently available epidemiological, biochemical, and clinical evidence” [1].David Siegel[1] http://lpi.oregonstate.edu/infocenter/paulingrec.html

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