Chapter Twelve


Mainstream Nutritional Science and the Unconventional Nutritional Cancer Therapies

Chapter Twelve

Can Vitamins and Minerals Help?

The Scientific View: Micronutrients

There seems to be little question among scientists that vitamins and minerals can prevent, inhibit, and occasionally accelerate some forms of cancer. They may also play a role in reversal of some forms of cancer. Research has also shown in animal and clinical studies that vitamins may enhance the effect of anticancer treatments such as radiotherapy and chemotherapy, may protect against their side effects, and may possibly extend the life of cancer patients who are treated jointly with mainstream therapies and vitamins. I believe that careful review of these provocative scientific studies should be of real interest to both people with cancer and health professionals who are considering nutritional supplements or dietary manipulations as a form of treatment or self-care.

Vitamin A, Retinoids, and Carotenoids

By far the most extensive research on diet and cancer has been made for the retinoids. “Retinoids” refer to vitamin A (retinol) and its isomers, derivatives (retinal, retinoic acid), and synthetic analogues. According to Peter Greenwald, Director of the Division of Cancer Prevention and Control at the National Cancer Institute (NCI), retinoids have the capacity to modify the cancer cell, in some cases actually causing the differentiation, or return to a normal state, of cancer cells. “Retinoids are of special interest for use in clinical prevention because they can exert their antineoplastic activity in cells that are already dedifferentiated or initiated into a malignant state [emphasis added].”1 In plain English, this means retinoids can sometimes stop the cellular process of loss of differentiation that characterizes the progression of cancer. This is of critical interest to people with cancer.

For example, researchers have found that vitamin A can suppress abnormal differentiation of prostate epithelial cells in laboratory tests after a potentially malignant state has been induced by chemical exposure or radiation. According to Greenwald, when the vitamin A was removed from the culture medium, “full expression of the malignant phenotype occurred.”2 And with human promyelocytic leukemia cells, retinoids returned malignant cells to full differentiation with the shape and biochemical characteristics of a healthy granulocyte.3

Other retinoids have “consistently arrested malignant progression in three different rodent bladder cancer systems” and have inhibited the development of cancer in chemically induced breast and skin cancer models. “Regression of chemically induced tumors and a delay in the appearance of transplanted tumors has been reported for several other synthetic retinoids.”4

Greenwald goes on to say that beta-carotene, a dietary precursor of vitamin A, is particularly interesting for cancer patients because of its very low toxicity and because of the fact that blood levels are directly related to dietary intake, whereas the blood levels of retinoids are strictly controlled.”5 Says Greenwald:

A direct chemopreventive role for beta-carotene has been suggested because of its very efficient ability to deactivate singlet oxygen and trap organic free radicals. … About 20 reports have evaluated cancer incidence and vitamin A or beta-carotene intake. In nine retrospective studies, a significant increase in cancer risk at various sites was associated with diminished vitamin A intake. Risks reported for groups with low vitamin A intake were about twice those for the high intake groups.6

The National Academy of Sciences Diet, Nutrition and Cancer report concluded: “Studies in animals indicate that an increased intake of this vitamin [A] has a protective effect against the induction of cancer by chemical carcinogens in most, but not all, instances.”7

In epidemiological studies, low vitamin A intake has been associated with increased risk of colon, lung, cervical, larynx, bladder, esophageal, stomach, colon and rectal, prostate, and oral cancers. Three reports based on data from cohort studies have found a general inverse relationship between serum levels of vitamin A and cancer in general–although higher levels of serum vitamin A have not yet been decisively linked to higher levels of vitamin A intake.8 For example, a study by Menkes and colleagues in the New England Journal of Medicine found a strong inverse correlation between serum beta-carotene levels and the risk of squamous cell carcinoma.9 Similarly, a study of diet and lung cancer which compared the dietary histories of 332 lung cancer patients with 865 controls found a clear negative association between dietary beta-carotene intake and risk of lung cancer.10 This finding is supported by a 1990 review of 12 studies by W.C. Willett at Harvard Medical School. In each study, high intake of fruits and vegetables containing carotenoids was associated with reduced risk of lung cancer, though this finding is also compatible with the possibility that some other factor in these foods is responsible for the result. At the same time, little relation was found between vitamin A intake and the risk of lung cancer.11

Vitamin A and retinoids have been demonstrated in clinical studies to reverse a variety of precancerous and cancerous conditions, primarily those related to epithelial tissue. In two clinical trials, the retinoid etretinate had a preventive effect on the recurrence of superficial bladder tumors and stimulated regression of bronchial metaplasias in smokers.12 Similarly, in a randomized clinical trial of patients with oral leukoplakia, a premalignant lesion associated with oral cancer, 13-cis-retinoic acid was demonstrated to reduce the size of lesions in 67% of those treated (vs. 10% of controls) and reverse dysplasia in 54% of those treated (vs. 10% of controls).13 This reversal of a premalignant lesion with a retinoid in humans is a dramatic finding.

As a result of the laboratory findings, the epidemiological studies, and the early clinical trials showing reversal of premalignant conditions and prevention of recurrence of some tumors, researchers have undertaken a broad range of intervention studies to test the efficacy of retinoids in the prevention and reversal of human cancers. In 1986, researchers at the NCI listed 19 “chemoprevention intervention studies” in which retinoids were being evaluated for their capacity to “prevent precursor lesions, reverse precursor lesions, reduce the incidence of malignancy, reduce mortality due to malignancy, and reduce total malignancy.”14

“Chemoprevention,” in other words, has become the polite label under which the capacity of nutrients not only to prevent but actually to reverse cancers and precancers entered the world of mainstream cancer research. As nutritional researcher Lawrence Kushi points out, the approach of mainstream researchers to the question of nutrition in cancer as characterized by the term “chemoprevention” is essentially “the attempt to place a medical paradigm on what is essentially a behavioral/lifestyle intervention, that is, dietary change.”15

One intriguing clinical study was reported by Frank L. Meyskens, Jr., then at the University of Arizona Cancer Center in Tucson:

Extensive laboratory investigations have documented that Vitamin A and its natural and synthetic derivatives (the retinoids) can inhibit proliferation and stimulate differentiation and/or maturation in normal and many transformed [e.g., cancerous] cells. Epidemiological studies also support the general notion that vitamin A is a natural inhibitor of the development of human cancer. These observations have prompted us to examine the role of retinoids as anticancer agents. We propose a general strategy which defines precancer and cancer as a continuum from normality to abnormality in which the modalities of prevention and treatment are blurred [emphasis added].16

Based on the laboratory research showing that retinoids acted as a differentiating agent in mouse and human melanoma cells, in 1978 Meyskens started, in an adjuvant trial, comparing BCG (attenuated bovine tubercle bacillus) injections alone with BCG plus vitamin A for stage I (high risk) and stage II malignant melanoma. At the time of publication in 1984 (based on the first 120 patients) those treated with BCG plus vitamin A were experiencing a “favorable” trend in relapse-free survival compared to those receiving BCG alone.17 A subsequent unpublished study by Meyskens failed to support his early findings. But the effort was sufficiently intriguing to merit this brief review (Frank L. Meyskens, Jr., personal communication, 1993).

Meyskens also reported “considerable antitumor activity” in a broad phase II clinical trial with several malignant and premalignant skin conditions using the retinoid 13-cis-retinoic acid. He found positive short-term responses in skin or subcutaneous cancers in patients with advanced metastatic head and neck cancers, and positive responses in 8 of 12 patients with T-cell lymphoma mycosis fungoides, “with four demonstrating nearly complete resolution of the disease.”18

The positive results in both experimental research and in the early clinical trial of vitamin A with melanoma, which the later study did not support, are particularly interesting in view of the fact that melanoma is reported to be one of the cancers that has responded most frequently to the Gerson alternative nutritional cancer therapy. The Gerson raw foods diet, with frequent ingestion of fresh vegetable juices, provides a very high intake of beta-carotene. I have personally known several melanoma patients who did well for periods of years on the Gerson program. On the other hand, the course melanoma takes is highly variable, and there may be, as I reported in chapter 10, an important psychological component in improved outcomes with this disease.

The B Vitamins

The National Academy of Sciences Diet, Nutrition and Cancer report said that the literature on the relationship of dietary B vitamins to the occurrence of cancer was inadequate to draw any conclusions.19 The committee wrote: “Because the B vitamins are essential components of any adequate diet and are necessary for the continued maintenance of cellular integrity and metabolic function, severe deficiencies in any of them will clearly reduce the growth rate of tumor cells and interfere with normal functioning of the organism.”20

Tannenbaum’s studies in the 1950s, which played a key role in establishing that “underfeeding” reduced the incidence and yield of tumors in animals, nonetheless found no significant differences in the frequency of tumors in animals fed high, medium, and low levels of B vitamins.21

As with other vitamins, the synergistic effects of specific B vitamins and other nutrients can be striking. In one study of mice with transplantable tumors, a combination of vitamins B12 and C inhibited the mitotic activity of the tumor cells and “produced a 100% survival rate, while neither vitamin alone at the same dosage had any effect.” The effect was specific to ascites tumors.22

On the other hand, vitamin B12 can also serve as a powerful tumor promoter. One researcher fed rats carcinogenic DAB (3,3é = diaminobenzidine) and then divided them into two groups, one of which received a vitamin B12 supplement while the other was on a diet that excluded the vitamin. The supplemented rats had a 78% incidence of liver tumors, while the unsupplemented rats had a 17% incidence. When methionine was added to the diets of both groups, the tumor incidence dropped to 33% and 11%, respectively. A control group that received vitamin B12 but was not exposed to the carcinogen developed no tumors. Several other researchers have confirmed these findings, which show how vitamin B12–so effective with vitamin C against mouse tumors in the previous study, and innocent of carcinogenic effects on its own–powerfully promoted tumor growth in the presence of a carcinogen, but was modified in this tumor-enhancing effect by the addition of another nutrient.23

Vitamin B6 is one of the most interesting B vitamins for cancer patients. Hans Ladner and Richard Salkeld, a team of German and Swiss researchers, reported an important controlled clinical trial in which 300 mg of pyridoxine (vitamin B6) was given throughout a 7-week course of radiotherapy to half of a group of 210 patients aged 45 to 65 with endometrial cancer.24 They found a 15% improvement in 5-year survival compared to patients who did not receive the supplement, and found no side effects from the supplementation. The theoretical basis for the study was animal experiments showing that healthy animals subjected to whole body radiation, or animals carrying tumors, developed tryptophan metabolism disorders that resembled those created by vitamin B6 deficiency states. In humans, these metabolic disorders resembling vitamin B6 deficiency states are found in Hodgkin’s disease, and bladder and breast cancer. One study suggested that vitamin B6 supplementation to correct the metabolic abnormality might prevent recurrence of bladder cancer.24 Ladner and Salkeld also “confirmed the beneficial effects of pyridoxine administration on radiation-induced symptoms–nausea, vomiting, and diarrhea–in gynecological patients treated with high-energy radiation, and observed that impairment of the vitamin B6 status was corrected by 300 mg pyridoxine daily.”

Ladner and Salkeld then studied vitamin B6 status in 6,300 gynecological cancer patients with cervical, uterine, endometrial, ovarian, and breast cancers. They found that before radiotherapy, in uterine, ovarian, and breast cancer, “the more the tumor had progressed, the more pronounced was the impairment of vitamin B6, B1 and B2 status. During the course of irradiation, the vitamin B status became progressively more impaired.” This led to their important findings that quality of life and survival were both improved with B6 supplementation. They also found that chemotherapy–doxorubicin, cisplatin, and cyclophosphamide–generated “no definite worsening” of vitamin B6 status in women with metastatic endometrial or breast cancer.25 This study of the improved quality of life for women with gynecological and breast cancer who use vitamin B6 supplements with radiotherapy is particularly provocative when we consider a similar report on vitamin C below.

Vitamin B6 has also been reported to be particularly effective in inhibiting melanoma cancer cells. Based on this experimental evidence, one research team developed a topical pyridoxal cream that, “when applied to patients with recurrent malignant melanoma, produced a significant reduction in the size of subcutaneous nodules and complete regression of cutaneous papules.” While the results were considered preliminary, “they are provocative and may lead to a more successful topical treatment of this highly lethal cancer.”26

Linus Pauling and the Controversy over Vitamin C

A major public controversy over the role of vitamin C in cancer has been waged ever since the double Nobel Prize laureate, Linus Pauling, endorsed high-dosage use of the vitamin for both cancer and the common cold. In 1976, Pauling and his Scottish colleague Cameron reported in the Proceedings of the National Academy of Sciences that they had conducted a study in which “hopelessly ill” cancer patients had been given 10 gm of vitamin C a day in divided doses. They reported that survival for more than a year after the date of “untreatability” was found in 22% of their experimental group but in only 0.4% of historical controls (past patients with similar diagnoses who did not take vitamin C). They also reported that 370 nonrandomized contemporary controls showed the same survival statistics as the historical controls.

Thunderous criticism of the study arose in the scientific community. Melvyn Werbach, M.D., of the UCLA School of Medicine summarized the criticisms: (1) lack of a prospective random double-blind study; (2) lack of rigidly defined criteria for “untreatability”; (3) failure to match patients by histological identification of type and origin of cancer cells; and (4) failure to ensure that cases and controls adhered to their medication schedules.27

At the Mayo Clinic, researchers conducted two experimental double-blind studies to determine whether the survival advantage that Pauling and Cameron had demonstrated would show up under what they considered optimal scientific conditions. The first study by E.T. Creagan and his colleagues randomized 150 patients with advanced cancer into two groups:

Sixty “evaluable” patients received vitamin C and 63 similar, randomized patients received a lactose placebo, while 27 of the randomized patients elected not to participate. Neither vitamin C nor the placebo improved survival times which averaged 51 days; however, those who withdrew survived only 25 days, raising the question of how the decision to withdraw may have influenced survival [emphasis added]. The authors note that, in contrast to the earlier Pauling and Cameron study, a large proportion of patients in this study had received radiation and/or chemotherapy.28

In the second effort at the Mayo Clinic to replicate or disprove the Pauling-Cameron findings, Charles Moertel (who had been second author on the first study) and colleagues conducted a randomized controlled double-blind study of 100 advanced large-bowel cancer patients who had not received chemotherapy and who were given either the 10 gm of vitamin C that Pauling recommended or a placebo for <%8>2<%0><$E{{up 38 1} /{fwd 12 2} } > months. There were no differences in survival between the two groups, although none of the patients on vitamin C died while they were taking the vitamin. Moertel et al. concluded: “On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.”29

Following publication of this study, its senior investigator Moertel went on network television to denounce vitamin C as “absolutely worthless.” Pauling responded by accusing the Mayo Clinic of making “false and misleading” claims about the study and asked for a retraction, correction, and apology from the New England Journal of Medicine, which had published the study. The editor refused. The journal also refused to publish two letters from Pauling and at least two other letters critical of the study. Evelleen Richards in the highly respected British journal New Scientist reported:

Pauling has never been content with unorthodox backing. He has consistently sought recognition of his claims from the establishment. Yet, in spite of his belief that the medical profession has never dealt with his claims in an unbiased and objective manner, his faith in the scientific method as the supreme arbiter of truth remains undiminished. Cameron, who describes his own professional background as “perfectly conventional, even conservative by some standards,” shares Pauling’s attitude. Cameron remains optimistic that once someone has demonstrated the “flaws” in the latest study from the Mayo Clinic, the National Cancer Institute will find a new trial. A fresh trial, he emphasizes, “must not be carried out by vitamin C enthusiasts nor by bigots, but by fair-minded physicians, and conducted not in secrecy but in open cooperation using a mutually agreed protocol.”

Therein lies the crunch. The idea of a cooperative approach embodying agreed criteria is not easily realized. Even if both sides to the dispute could agree about how to evaluate their respective claims about vitamin C, recent studies in the sociology of scientific knowledge suggest that impersonal rules of experimental procedure do not necessarily resolve disputes about “facts” and their interpretation. Such studies indicate that it is not always possible to dissociate the design of an experiment from the commitments of those who frame and evaluate the experiment. This latest chapter of the controversy over vitamin C tends to support this sociological contention. On the most superficial analysis, the Mayo Clinic’s team is simply not talking the same language as Cameron and Pauling.

Throughout, Cameron and Pauling have emphasized that the massive doses of vitamin C that they recommend (10 grams or more daily) are essential to patients with cancer, who show an increased need for this vitamin. They say that, unlike conventional chemotherapy, vitamin C restrains rather than kills cancer cells, and that vitamin C plays a vital part in stimulating the immune system, improving the general health and well-being of the patient. Pauling and Cameron are not, therefore, offering a “cure” for cancer, although they have described some cases that seem to deserve this label. What they would expect, on the basis of their studies, is that, in patients given vitamin C, tumors would grow less quickly and some of the distressing symptoms of cancer would be alleviated. These patients would survive slightly, but significantly, longer and enjoy better quality of life. Cameron and Pauling also point out that vitamin C does not have the debilitating side effects of conventional chemotherapy, and that it is not expensive and does not need elaborate equipment.

Richards then reviewed Pauling and Cameron’s critique of the methodological problems of the study of Moertel et al. First, urine tests for vitamin C levels were not routinely done, and those that were done indicated that at least one of the controls was found to be taking vitamin C independently. Second, in the Mayo Clinic study, vitamin C was stopped as soon as tumors started to grow again, which worked out to a median time of 10 weeks. In the Cameron-Pauling studies, vitamin C was continued indefinitely. “So the effect observed was related not only to the question of whether or not the tumor began to progress, but also to the subsequent rate at which the tumor grew under continued administration of vitamin C, and to any effect on the patient’s general health that might contribute to his or her capacity to resist death from cancer.”30

Third, and perhaps most important, Pauling and Cameron were concerned with the “rebound effect.” Said Richards:

If someone suddenly stops taking large doses of vitamin C, the level of vitamin C circulating in their body drops to well below normal. Doctors have known about this effect for about 12 years. Pauling and Cameron have repeatedly warned patients of its possible dangers. They believe the resultant temporary depression of the immune system may induce tumors to grow more quickly. The Mayo Clinic’s team either ignored or was unaware of this possibility. The clinic’s doctors abruptly discontinued vitamin C for those patients who showed signs that a tumor was progressing, thus inducing the rebound effect. According to Pauling and Cameron, this oversight invalidates the clinic’s study; they say that the study does not refute their findings. They even suggest that the combination of the rebound effect and the subsequent highly toxic chemotherapy may have shortened the lives of patients participating in the Mayo Clinic’s study.

Irrespective of the cogency of Pauling and Cameron’s criticisms, the clinic’s study clearly demonstrates how vested interests intrude on the evaluation of treatments. At the beginning of the study, the team at the Mayo Clinic conceded that the powerful cytotoxic drug fluorouracil (either alone or in combination) was of no value in the treatment of colorectal cancer. Yet it fell back on this treatment for more than 50 per cent of patients in the study when it found vitamin C ineffective by the same criteria. The doctors’ preference was for a treatment which is professionally controlled and administered and fits the established theoretical framework: yet this treatment is therapeutically useless and highly toxic. … In the face of the Mayo Clinic’s own evaluation of this treatment, it is difficult to justify the decision, which Moertel subsequently defended on ethical grounds, to withdraw vitamin C or placebo and substitute chemotherapy for so many patients. …

In spite of the orthodox medical profession’s repeated emphasis on the need properly to evaluate Cameron and Pauling’s research, most chemotherapies for cancer, including fluorouracil, have been widely applied in practice without previous evaluation by randomized controlled trials. Several studies have demonstrated that, once a therapy is professionally adopted and endorsed, there are significant financial, public and professional obstacles in the way of abandoning it, even if it is demonstrated to be ineffective and to harm patients.31

Adherents of Pauling’s position have thus been able to argue, with some legitimacy, that neither of the two Mayo Clinic studies actually tested Pauling and Cameron’s thesis–the first because patients were pretreated with chemotherapy and the second because (a) controls were not adequately tested for “out-of-study” use of vitamin C; (b) vitamin C was withdrawn as soon as tumors began to grow, thus possibly initiating a “rebound effect”; and (c) subsequent chemotherapy may have compromised survival.

While the mainstream scientific community has stuck close to the current consensus position that the Mayo Clinic studies “disproved” any positive role for vitamin C in cancer treatment, the most recent edition of the authoritative nutrition text edited by Maurice E. Shils and Vernon R. Young, Modern Nutrition in Health and Disease, gives two very different treatments to the vitamin C and cancer controversy, depending on which section you read. Shils, in his overview of nutritional approaches to cancer, dismisses the whole controversy in a paragraph without mentioning Pauling’s work or the critique of the Mayo Clinic studies: “Ascorbic acid in the high dose of 10 g daily had no advantage over a placebo in 100 patients with advanced colorectal cancer who had no previous chemotherapy. The double blind study indicated no difference in the progression of measurable disease or survival. The same group had demonstrated earlier that this vitamin had no advantage over placebo when given in conjunction with chemotherapy.”32

But, in the same book, Hornig and his co-workers in their chapter on vitamin C give Pauling’s work a more subtle treatment. After describing Pauling’s study and the two Mayo Clinic studies, they take note of the controversy with the use of understatement and strategic placement characteristic of many scientists: “An exchange of views about this controversy has been published.” They then go on to describe a Japanese study showing increased survival with high-dose vitamin C. The Japanese study that they describe here, though flawed, lends weight to the Pauling position:

Observation of terminal cancer patients in two hospitals who were receiving either a low-dose ascorbate (4 g daily or less) or high-dose ascorbate (5 g daily or more) showed a significantly higher median survival of 105 days in the high-dose group compared to 35 days in the low-dose group. The administration of ascorbic acid seemed to improve the well-being of many cancer patients, as measured by decreased requirement for pain-controlling drugs, improved appetite, and increased mental alertness. However, these studies were poorly controlled, and the classification of “low dose” and “high dose” was arbitrary. Furthermore, the site of primary tumors seems to be important for the effectiveness of ascorbic acid; uterus and stomach are the most promising. In vitro, an inhibitory effect of ascorbic acid on the growth of human melanoma cells was demonstrated. In 1 mmol ascorbate, no melanoma colonies were observed and in 0.6 mmol ascorbate, the ability of melanoma cells to form colonies was 10 to 20 times less than for normal human amniotic cells. Again, additional controlled studies are needed to eventually establish a role for vitamin C in cancer [emphasis added].33

This gives you a taste of the public controversy over vitamin C. Note especially that some of the foremost authorities on vitamin C research are now more open to the potential for vitamin C in cancer treatment.

Cancer Prevention and Vitamin C

Epidemiological studies demonstrate an indirect association (indirect because they analyze foods known to contain high levels of vitamin C, not vitamin C itself) between high vitamin C intake and a lowered risk of cancer, particularly cancer of the esophagus and stomach. High consumption of fresh fruit specifically has been shown to protect against gastric cancer. A case-controlled study of vitamin C consumption and uterine cervical dysplasia, a premalignant condition, also showed a protective role for vitamin C; but a case-controlled study of colon cancer did not.34 Note that in the Japanese study cited above, stomach and uterine cancer were considered the best responders to vitamin C therapy.

More recently, 33 of 46 epidemiological studies surveyed by Gladys Block, Ph.D., of the NCI showed significant protective effects of vitamin C. In aggregate, those in the top fourth of vitamin C intake had approximately half the cancer risk of the lowest fourth in terms of vitamin C consumption. Twenty-one of 29 studies assessing fruit intake demonstrated a protective effect, particularly for cancers of the esophagus, larynx, oral cavity, pancreas, stomach, rectum, and cervix. Block concluded that: “While it is likely that ascorbic acid, carotenoids, folate and other factors in fruit and vegetables act jointly, an increasingly important role for ascorbic acid in cancer prevention would appear to be emerging.”35

A recent combined analysis of 12 case-controlled studies by Geoffrey Howe at the National Cancer Institute in Canada found that fruit and vegetable intake, and most notably vitamin C intake, provided a consistent protective effect for breast cancer. Howe concluded that if North American women increased their fruit and vegetable intake to reach an average 380 mg/day of vitamin C from those sources, the breast cancer risk in the population would be decreased by 16%.36

One aspect of the protective effect of vitamin C may lie in its ability to inhibit the oncogenic transformation of cells. Richard Schwarz of the University of California at Berkeley demonstrated that the presence of vitamin C in a culture of primary avian tendon cells and oncogenic Rous sarcoma virus “stabilizes the normal state [of the cells] by reducing virus production and promoting the synthesis of differentiated proteins.”37

Experimental evidence demonstrates that vitamin C can also inhibit the formation of carcinogenic nitrosamines, which are found in tobacco smoke, marijuana, some cosmetics, corrosion inhibitors, rubber products, rubber nipples for baby bottles, and cured meats. Precursors of nitrosamines are found in many foods: they react with sodium nitrite, a food preservative, to form carcinogenic nitrosamines in the acidic environment of the human stomach.38 Since vitamin C can inhibit the formation of nitrosamines in the stomach, this is widely assumed to be the basis for its protective effect against gastric cancers specifically.

This capacity of vitamin C to reduce nitrosamine levels in the stomach was demonstrated with esophageal cancer patients in a study performed in northern China’s Lin-Xian province, an area where esophageal cancer is common. Researchers measured levels of nitrosamines in the stomach and lesions in the esophageal epithelium, and found a positive correlation: the higher the nitrosamine levels, the more lesions were found. They then gave experimental subjects 100-mg vitamin C supplements three times a day, an hour after meals. They found a marked decrease in urinary nitrosamine products, which became comparable to those in people in areas with low esophageal cancer risk.39

Another protective aspect of vitamin C is its antioxidant activity. This discussion of vitamin C is an appropriate place to describe briefly the broader question of how vitamin C, selenium, and other antioxidants, several of which we discuss below, protect the organism against the wonderfully named “free radicals.”

Free radicals are potentially carcinogenic compounds created by both healthy and diseased cells in the course of cell respiration and intermediary metabolism. According to Carmia Borek of the departments of pathology and radiology at Columbia University College of Physicians and Surgeons:

The cellular oxidant state is of the utmost importance also in cellular protection against the oncogenic potential of radiation and chemicals. … Inherent cellular factors comprised of enzymes, vitamins, micronutrients and low molecular weight substance are protectors. These include superoxide dismutase and catalase, peroxidases and thiols, vitamin A, vitamin C, and vitamin E and the micronutrient selenium [emphasis added]. These antioxidants serve to defend the cells against elevated levels of free radicals produced by radiation, chemical carcinogens and tumor promoters. The free radicals … to varying degrees damage the cell.40

Borek summarizes the field as follows:

Free radicals are continuously produced by living cells. … Under optimal cellular metabolic conditions cellular antioxidants are sufficient to impart protection against oxidant stress. However, under conditions of exposure to carcinogens or to unfavorable metabolic stress which enhances free radical levels, inherent protection may prove to be inadequate leading eventually to neoplastic [cancerous] transformation. … Under stressful conditions cells require the external addition of antioxidants to enable them to cope with the excess load of free radicals and to minimize the oxidative damage and oncogenic transformation. Some nutrient antioxidants act directly, other agents such as selenium will impart their protection by inducing high levels of inherent protective enzyme systems which destroy peroxides. This enables the cell itself to increase its scavenging powers and to cope with the “overload” of free radicals and their toxic products thus preventing the onset and progression of malignant transformation.41

Two antioxidant enzymes, superoxide dismutase (SOD) and superoxide catalase, are also of interest in some alternative cancer therapies. These substances form part of the antioxidant cellular defense system against free radicals.

The role of vitamin C as one of the primary defenses against oxygen radicals is described by Etsuo Niki at the University of Tokyo: “Free radicals attack lipids, proteins, enzymes and DNA to eventually cause a variety of pathological events and cancer. … When aqueous radicals were generated in the whole blood, ascorbic acid [vitamin C] scavenged them faster than any other antioxidants [emphasis added] and protected lipids and proteins more effectively than bilirubin, uric acid or tocopherol (vitamin E).”42

Similarly, Balz Frei and Bruce Ames at the University of California at Berkeley investigated the effectiveness of selected antioxidants in human blood plasma. Ascorbic acid proved to be the most effective of all the antioxidants they tested and the only one which could prevent the initiation of lipid peroxidation, rather than simply lowering the rate at which the process occurs. They also found that the effect increased with the plasma concentration of ascorbic acid.43

Another pathway for the protective effects of vitamin C was proposed by Joachim Liehr at the University of Texas Medical Branch who found in animal studies that vitamin C may also play a role in inhibiting estrogen-induced carcinogenesis by reducing concentrations of metabolic byproducts of estrogen.44 The potential effects of vitamin C are closely related to dietary iron. According to Swiss researcher Alfred Hanck:

Iron deficiency is an aggravating factor in cancer patients. … Only ferrous iron is absorbed and ascorbic acid converts food ferric iron to bioavailable ferrous iron. … Vitamin C improves hemoglobin status and thus oxygen supply of tissue, with an increase in oxidative energy production. … The cytotoxic effect of ascorbic acid against malignant cells is significantly increased by chelation with ferrous iron. … This increased efficacy is attributed to the longer half-life of the ascorbate iron complex during cell contact compared to ascorbic acid.45

Vitamin C Inhibits Growth in Human Tumor Cell Lines

Vitamin C has also been shown to demonstrate an inhibitory effect on tumor growth. In an important 1989 study,46 a group of Belgian researchers reported in Cancer that sodium ascorbate (vitamin C) and vitamin K3 were administered separately and in combination to human breast, oral, and endometrial cancer cell lines. While both had an inhibiting effect on cancer cell growth at high concentrations, combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at much lower concentrations where vitamins given separately are not toxic. The inhibitory effect was suppressed by the addition of catalase to the culture, which suggested that the observed effect on cancer cells was connected to the formation of hydrogen peroxide.46 This study is obviously rich in possibilities for clinical trials of the combined vitamins. It has further interest because the presumed mechanism of the synergistic effect of these vitamins is hydrogen peroxide production. Hydrogen peroxide has long been a chemical of interest among some practitioners of alternative cancer therapies.

Other studies have demonstrated that stress linked to cancer lowers plasma levels of vitamin C in patients and in experimental animals. This has been demonstrated recently in patients with uterine, cervical, and ovarian cancer, and in leukemia and lymphoma patients.47 If cancer stress lowers vitamin C levels, and below-normal vitamin C levels diminish immune function, this would appear to be an additional rationale for vitamin C supplementation in cancer.

Vitamin C Is Helpful with Radiation and Chemotherapies

Apart from the controversy over the Pauling-Cameron studies, the most important report I have seen on vitamin C is a trial showing the benefits of vitamin C when used in conjunction with radiotherapy. Hanck reviews the literature and describes the study:

During radiotherapy, decrease of several vitamin levels [including] vitamins E, B12, folic acid and C have been observed. A decrease of vitamin C plasma levels due to irradiation treatment has been reported by several investigators. In addition, potentiation or augmentation of the lethal effect of radiation against tumor cells was demonstrated when ascorbic acid was co-administered [emphasis added]. Recently the effects of radiation therapy with adjunct ascorbic acid treatment have been investigated in 50 cancer patients in a prospective clinical trial. The patients were divided into two groups by random allocation. [Patients had cancers of the tongue, tonsil, cervix, esophagus, neck, skin, lip, and cheek, and Ewing’s sarcoma.] … Progressive disease was seen after one month in 5% of the control group and 3% of the study group. These values had increased to 20% of the control group after 4 months and 7% in the study group.

Based on 20 cases, Hanck found 45% of the control group surviving without disease and 50% with disease at 6 months; and 67% of the vitamin C group surviving without disease and 33% with disease at 6 months. He also found that, with the administration of vitamin C, patients suffered less anemia, less pain, less loss of appetite and weight. All the side effects of radiotherapy tended to be fewer. And since it is tolerated extremely well, he also urged further clinical investigations of the effects of high doses of vitamin C.48

In a related study, Paul Okunieff of Massachusetts General Hospital also found vitamin C to protect both the skin and bone marrow against the effects of radiation. It was not found to be toxic to the tumor itself, nor did it protect the tumor from radiation.49

Another potentially significant finding for cancer patients is the protective effect vitamin C has displayed against potential damage to the heart by Adriamicin (ADR, doxorubicin) in animal studies. According to Kan Shimpo and his colleagues at the Fujita Health University in Japan,

One possible mechanism of ADR-induced toxicity is the induction of peroxidation in cardiac lipids. Ascorbic acid is a potent antioxidant. Thus, the lipid peroxidation and cardiac toxicity of ADR are expected to be reduced by prior treatment of the animals with ascorbic acid. … Ascorbic acid … significantly prolonged the life of mice and guinea pigs treated with ADR. … The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.50

Experimental studies by Kedar N. Prasad of the University of Colorado Health Science Center have also demonstrated that two forms of vitamin C, sodium L-ascorbate and sodium D-ascorbate, enhanced the effectiveness of radiotherapy and the chemotherapeutic agents 5-fluorouracil (5-FU) and bleomycin when used on mouse neuroblastoma cells but not on rat glioma cells.51 When one reads the experimental research literature on nutrients and cancer, it is replete with descriptions of studies where vitamins acted on one cell line but not on another, or even in opposite ways in different cell lines.

Vitamin C May Help or Harm with Leukemia

The complexity of the question of just how nutrients affect cancer cells is underscored by an experiment that suggests a significant potential hazard in using vitamin C for some people with leukemia–but a significant possible benefit for others. Vitamin C has an apparent paradoxical effect in cell cultures from cancer patients with acute nonlymphocytic leukemia and preleukemia, or myelodysplastic syndrome (MDS). A study by Chan H. Park at the University of Kansas found that L-ascorbic acid and glutathione (which potentiates the effects of L-ascorbic acid) enhanced leukemia cell growth in samples from one third of the patients, suppressed leukemia cell growth in one sixth of the patients, and had no effect on the rest. It is intriguing that the effect was replicable: in repeated trials, cell cultures from affected patients responded in the same way, either toward enhancement of growth or suppression of growth. The ascorbic acid compound used in the experiment also enhanced cell growth in 24% of the normal control cell cultures.52 Park and Bruce F. Kimler also found that the reported effects of L-ascorbic acid had prognostic value for patients with MDS; patients sensitive to L-ascorbic acid have shorter survival times than patients who are not sensitive. The authors conclude that MDS is the ideal disease for in vivo trials to investigate the control of the disease process through L-ascorbic acid manipulation. Such trials are currently being planned.53

This suggests that leukemia patients considering experimenting with vitamin C therapy should do so only in careful collaboration with oncologists, preferably after ascertaining that their tissue culture was one of the minority that responds positively to vitamin C. The experiment, however, has the broader implication that different patients with the same histological type of cancer may respond in different directions to the same nutrient. The finding that vitamin C enhanced normal cell growth in 25% of the control cell cultures from healthy people is also intriguing. It is important to emphasize that a laboratory study of the effect of vitamin C on a cell culture does not predict how the vitamin will act on the cancer cells in a patient. But, for the many cancer patients who consider taking vitamins on their own–or on the advice of clinicians unfamiliar with the research literature–the potential hazard of vitamin C to patients with leukemia is worth noting. Above all, as Hippocrates said, never do harm to anyone.

In its summary of vitamin C research in 1982, the National Academy of Sciences report said that “the limited evidence suggests that vitamin C can inhibit the formation of some carcinogens and that the consumption of vitamin C-containing foods is associated with a lower risk of cancers of the stomach and esophagus.”54 Since then, the literature has continued to add intriguing and potentially significant pieces. The controversy over whether vitamin C extends life in cancer patients with advanced metastatic disease is scientifically unanswered due to the deficiencies of both the Cameron-Pauling studies and the replication studies. But the Japanese study, though flawed, again supports the Pauling hypothesis.

The Hanck study, although conducted with a mix of different tumor types, raises the real possibility that vitamin C may both extend survival and enhance the effects and diminish the side effects of radiotherapy. The Park laboratory experiment on human leukemia cell lines, on the other hand, emphasizes that in leukemia, at least, vitamin C may represent a hazard for some patients, while it may be helpful to others. And the study of vitamin C and vitamin K3 administered synergistically in breast, oral, and endometrial cell cultures suggests that the yield of a chemotherapeutic use of these vitamins might be much higher if they were given together.

Vitamin E May Help with Cancer, Chemotherapies, and Radiation

The summary of the National Academy of Sciences Diet, Nutrition and Cancer report on vitamin E was brief: vitamin E (specifically alpha-tocopherol), like vitamin C, inhibits the formation of carcinogenic nitrosamines. But the committee found no reports indicating an effect of vitamin E on nitrosamine-induced cancers. Limited experimental evidence in several studies, however, showed that vitamin E inhibited tumor development.55 But this short summary greatly understates the potential significance of vitamin E for cancer patients.

First, while both vitamin C and vitamin E (alpha-tocopherol) block the formation of carcinogenic nitrosamines and reduce levels of fecal mutagens, they work better in combination than they do independently to reduce fecal mutagen levels. Similarly, while vitamin E had no independent effect on chemically induced cancers in animals, it enhanced the preventive effects of selenium.56 Second, some forms of vitamin E are effective in reducing growth and enhancing differentiation in mammalian cancer cells. Prasad, one of the leading authorities on vitamin E, has demonstrated that, among the several forms of vitamin E, vitamin E succinate appears to be the most effective in reducing growth and enhancing differentiation of mammalian cancer cell lines in laboratory experiments, perhaps because “tumor cells pick up this form of vitamin E more readily than they do other forms.”57 Third, high-dose alpha-tocopherol has reduced growth of human neuroblastoma cells in living cancer patients, and has reduced benign mastitis (inflammation) of the breast.58 Fourth, and very important, vitamin E enhances the effectiveness of some chemotherapies, radiation, and hyperthermia on cancer cell lines. According to Prasad:

Vitamin E enhances … the effect of ionizing radiation on tumor cells in culture without affecting the radiation response of normal tissues. Vitamin E also enhances the effects of hyperthermia on tumor cells in culture, and inhibits the production of prostaglandin E series which are known to suppress the host’s immune system. Finally, vitamin E reduces the toxic effects of some chemotherapeutic agents. These studies suggest that vitamin E may be one of the important anticancer agents which could play a very significant role in the prevention and treatment of cancer.59

In animal studies, vitamin E has been shown to reduce cardiac and skin toxicity from doxorubicin, and lung fibrosis related to bleomycin–two very widely used chemotherapies.60 In addition to protecting the heart against damage from doxorubicin in animal studies, vitamin E has been reported to have a possible protective effect in humans against hair loss from doxorubicin therapy. Werbach summarizes a study by Wood in the New England Journal of Medicine: “69% of patients on doxorubicin [Adriamicin] receiving 1600 IU dl-alpha-tocopherol acetate [vitamin E] daily did not develop alopecia [hair loss]. Thoseêwho did develop alopecia were believed to have received the vitamin E too late before chemotherapy, as it should be started 5-7 days prior to commencement.”61

These vitamin E studies represent, in my judgment, stunning examples of the underutilization of scientific nutrition in cancer. Each year, hundreds of thousands of women around the world take doxorubicin at the same time that they undergo breast surgery. They not only undergo the personal loss of part or all of their breast, they also lose their hair. In addition, many end up with heart damage, a known side effect of doxorubicin in many situations. If vitamin E in an admittedly preliminary study was shown to protect against hair loss with doxorubicin, why has this study not been replicated as a real priority in cancer research? Further, since animal studies show that it may protect against heart damage, why does this not add an even stronger argument for full replication? I can see no good answer to these questions. If some oncologists maintain that we do not yet have enough evidence to recommend to patients undergoing doxorubicin treatment that they take vitamin E, then getting that evidence should be a national research priority. If others answer that there is already sufficient evidence to recommend taking vitamin E with doxorubicin, that raises the equally troubling question of why most patients are not told they should take vitamin E when undergoing this therapy. For the biomedical cancer researcher, protecting women against hair loss when fighting for their lives with breast cancer may seem trivial. But for the patient-centered medical practitioner, protecting women with breast cancer against hair loss is not at all trivial. Hair loss makes a profound difference in the suffering that women undergo. Therefore, if this is a preventable problem, it should be a vital matter to conduct the inexpensive and innocuous research that would settle the matter of hair loss and vitamin E and make the outcome a standard element in doxorubicin protocols. But even for the strictly biomedical researcher, unconcerned with hair loss, the issue of preventing heart damage with vitamin E should have some real salience. Again, the studies would be inexpensive and potentially lifesaving.

Finally, it is worth remembering that many of the salutary effects of the antioxidant vitamins A, C, and E on cancer, according to Prasad, are achieved best by their synergistic interactions.62 Thus, studies of the individual nutrients may understate their potential for suppressing cancer cell growth, encouraging cell differentiation toward normality, enhancing immune function, potentiating the effects of existing anticancer therapies, and protecting the organism from the harmful side effects of some of these therapies.

Minerals and Cancer

Minerals play a role in both the enhancement and inhibition of human cancers. We will look at the evidence on selenium and zinc. Selenium is important because of its broad anticancer effects. Zinc is important because it is an antagonist to selenium and may in itself enhance or inhibit different tumors.

Selenium in minute quantities is essential to human health. According to Prasad, among the minerals, “only selenium has been shown to have a role in cancer prevention”:

Like vitamin E, selenium acts as an antioxidant and strengthens the body’s immune defense system. Thus, many of the effects which are produced by vitamin E deficiency can be reversed or prevented by selenium. Some laboratory experiments have suggested that the combination of vitamin E and selenium is more effective in preventing cancer than either of them alone.

Certain metals such as lead, cadmium, arsenic, mercury and silver block the action of selenium. … Recent laboratory experiments have shown that high doses of zinc block the action of selenium. Therefore, one has to be careful about taking excessive amounts of zinc (over 20 milligrams per day from diet and supplements) while taking selenium [emphasis added].

Protein-rich and unsaturated fat-rich diets have been shown to increase the selenium requirements of the body. …

Commercial preparations of selenium include inorganic selenium (sodium selenite) and various organic compounds of selenium. It has been reported that sodium selenite is not absorbed adequately, whereas organic selenium, including yeast-selenium, is absorbed very well. For this reason, yeast-selenium is considered best for human consumption. … It has been reported that selenium doses of about 250-300 micrograms a day (diet and supplements) would be helpful in preventing cancer. If an average person consumes 125 to 150 micrograms of selenium a day, an additional supplemental amount of 100 micrograms is unlikely to produce any major side effects.63

One of the foremost selenium investigators, Gerhard Schrauzer of the University of California at San Diego, says:

Apart from its functions as an essential micronutrient, selenium also appears to have other physiological functions in which it acts as a physiological resistance factor [emphasis added]. Its cancer protecting effects fall into this category. In addition, selenium protects against free radicals, mutagens, toxic heavy metals and certain bacterial, fungal and viral pathogens. The selenium requirement increases under stress, just as the requirement for certain vitamins increases during infections.64

Selenium, according to Schrauzer, is most effective as a form of nutritional cancer prophylaxis. In animal research, its protective effect is greater the earlier in life it is given, and its shielding effect against virally induced cancer disappears if the nutrient is no longer fed to the animal. Nevertheless, selenium does have an effect on slowing the rate of growth of established spontaneous or transplanted breast tumors in animals, and in reversing the development of some malignant cell lines when used at pharmacological levels.65 Further, selenium has shown a general capacity to stimulate the immune system in several animal models, which may add to its anticancer effects.66

It is of special relevance to cancer patients undergoing chemotherapy that selenium “has by now been shown to prevent or retard tumorigenesis induced by virtually all the major known carcinogens,” probably, Schrauzer believes, “by modulating the rate of cell division.”67 For those undergoing radiotherapy, research by Carmia Borek is of interest: she found that pretreatment of a mouse cell line with nontoxic levels of sodium selenite “inhibits the induction of malignant transformation by x-rays” as a result of the ability of selenium “to induce high levels of free radical scavenging systems in the cells exposed to the oncogenic agents.”68 She writes:

There is a close interrelationship between selenium and vitamin E in their antioxidant actions. However, the role of vitamin E as an anticancer agent varies with the model studied and probably depends on the tissue content of the vitamin. We found selenium to be a true protector. Its maximum effectiveness was imparted when cells were preincubated with the trace element. Thus, selenium can serve as a true radioprotective and chemoprotective agent.69

Zinc, like selenium, is widely taken as a supplement by many people interested in nutritional supplements. A mineral that is essential to life, it plays a key role in cell replication, tissue repair, and growth. Zinc-deficient children are frequently small in stature. Marginal zinc deficiency is suspected to be quite widespread in the United States. Pronounced zinc deficiency depresses immune function in both humans and animals.70

Zinc can both enhance and retard tumor growth. In epidemiological studies, the National Academy of Sciences report described a study in England and Wales where gastric cancer was higher in people whose gardens had high zinc levels in the soil. Schrauzer and his colleagues examined food intake in 27 countries and reported a direct correlation between higher zinc intake and a higher incidence of leukemia and cancers of the intestine, breast, prostate, and skin. They concluded that zinc increases cancer risk by its known antagonism to selenium. Schrauzer also found that high zinc in blood samples collected from healthy donors across the United States correlated directly with mortality rates from large bowel, breast, ovary, lung, bladder, and oral cancer in the different areas where the blood was collected. Zinc and selenium levels in the blood were inversely related. On the other hand, two studies of esophageal cancer found zinc levels to be lower in the diet of countries where that cancer is common and lower in the blood of patients with esophageal cancer than in normal controls. Clearly, in the latter studies, “the altered zinc levels may have followed, rather than preceded, the onset of cancer.”71

The experimental evidence collected in the National Academy of Sciences report supports the epidemiological evidence, showing both the enhancing and retarding effects of zinc on tumor growth:

Zinc deficiency appears to retard the growth of transplanted tumors, whereas it enhances the incidence of some chemically induced cancers. In some experiments, dietary zinc exceeding nutritional requirements has been shown to suppress chemically induced tumors in rats and hamsters, but when given in drinking water it counteracts the protective effect of selenium in mice. These data are insufficient to explain the effects of zinc and of interactions between zinc and other minerals on tumorigenesis.72

While the evidence on the effect of zinc on tumor development is complex, it strongly suggests that, in general, one should be cautious about taking zinc supplements if one has cancer. And since selenium has a wide spectrum of demonstrable anticancer effects, cancer patients should be particularly cautious with zinc, since it is a selenium antagonist. I have seen many cancer patients taking moderately large amounts of zinc as part of a comprehensive megavitamin nutritional supplement program. In view of the available scientific evidence, this is another critical example of an area where uninformed nutritional supplementation may do harm.

Allergy, Food Sensitivities, and Cancer

Early in the twentieth century, mainstream medicine in America had a significant interest in food allergies and sensitivities. This interest diminished drastically as modern pharmaceutical research created the potential to control many allergic reactions with antihistamines, and the field of allergy research moved from the clinician’s office into the laboratory. As the new focus on laboratory research on antigen-antibody interactions developed, a splinter group of allergists called “clinical ecologists” broke off from the mainstream and kept their focus on empirical relationships between foods and other allergens and clinical responses to them. Moreover, the clinical ecologists came into existence just as the petrochemical revolution after World War II was sweeping through the American economy, creating a whole new realm of chemical exposures for the American public that no medical specialty was addressing adequately. So the clinical ecologists added an empirical interest in chemical sensitivities to their interest in food allergies and other allergenic problems.

The clinical ecologists remain an “alternative” medical group, largely despised by their mainstream colleagues. As with many other splinter groups, the clinical ecologists attract many “true believers” who make excessive claims for the field. Yet in my judgment the clinical ecologists are pursuing an important line of inquiry concerning patterns of human reaction to foods, chemicals, and other substances.

In mainstream nutritional research, the relationship of allergies to cancer is a minor, yet potentially significant issue. The central question raised is whether allergies may have a protective effect against development of cancer or predispose people to it. A 1988 report by William McWhorter of the NCI summarizes the research from a series of studies over the last three decades: “Thirteen [studies] reported allergy to be protective, three found no association, and two foundêallergy to be a risk factor. The hypothesis often given to explain a protective effect is that individuals with allergies may have hyperstimulated immune systems, which are better able to detect and eliminate incipient malignancies.”

McWhorter reported a prospective study of 6,108 adults surveyed during 1971-75 in the First National Health and Nutrition Examination Survey.73 His objective was to focus on the relationship between a history of allergy and the subsequent risk of developing cancer. The group with allergies–those who had been told by a physician that they had asthma, hay fever, hives, food allergy, or any other allergy–constituted 30.1% of the sample, or 26.3% if the category was restricted to those who had allergic histories of more than 5 years. He found that allergy sufferers–controlling for race, sex, age, and smoking history–had a “highly significant positive association between history of any allergy and development of any cancer.” A family history of allergy was also a risk factor for subsequent cancer.

Breaking down the allergies into specific subgroups, and the cancers into specific diagnoses, McWhorter found that the strongest cancer association was with hives and “lymphatic and hematopoietic malignancies, which included leukemias, lymphomas, and myelomas [emphasis added]. … The adjusted risk factor of developing a lymphatic-hematopoietic malignancy for persons with hives was particularly strong.”73

This study is, the author notes, the first prospective study that controls for age, sex, smoking, and race, and the first based on a population derived from a national probability sample. The limitations of the study included the small numbers of people with specific allergies and specific cancer types, and the very real possibility that allergic symptoms were underreported by people with higher cancer risk–nonwhites, smokers, males, and older people.74

In Modern Nutrition in Health and Disease, Maurice Shils supports McWhorter’s findings in one significant area: he reports on a series of studies which document an increased risk of intestinal lymphomas among patients with celiac syndrome. Celiac syndrome is an allergy or hypersensitivity to the gliadin fraction of grain protein gluten. Three separate studies reviewed by Shils found a very high incidence of intestinal lymphomas in a series of celiac patients: 10% in one study, 6.2% in a second, and 6.9% in a third: “Because of this relationship, lymphoma should be suspected with the onset of celiac syndrome in middle age especially, but also in young people particularly with certain racial backgrounds. Males above 40 years of age with long-standing celiac syndrome who are not eating a gluten-free diet are a major risk group [emphasis added].75

To this, I would add some personal and clinical notes. I have a special interest in this subject because my father developed an intestinal non-Hodgkin’s lymphoma and my brother was born a celiac syndrome child. I developed a celiac condition when I was 40, accompanied, when uncontrolled, by hives, and my son has also been diagnosed with a wheat allergy which may well reflect broader celiac sensitivity. I have strong reason to suspect an undiagnosed celiac condition in my father, based on a lifelong history of skin rashes similar to those my brother and I experience when we do not follow a celiac diet. To my knowledge, lymphoma patients (including Hodgkin’s disease patients) are rarely, if ever, informed of the high incidence of celiac syndrome preceding lymphoma. I wonder–as I do with other nutritionally related cancer research–whether a diet that may well prevent the development of lymphomas might play some adjunctive role in controlling an established lymphoma, particularly when there is a history of celiac disease.

I would hypothesize further that allergy may play a protective role against some cancers–especially in certain phases of an allergic life history–but that it might play a contributing role at other times or for other cancers. Borrowing from Hans Selye’s stress studies, some allergists believe that allergies may stimulate the immune system for a considerable period of time, but that sustained stress over long periods (including allergic stress) may result ultimately in depleted resilience. Thus, the allergy might be protective in an earlier period of life, but if allergies and other stresses exhaust immunocompetence in later life, it might become a risk factor. One finding in the McWhorter study is intriguing in this regard: the one age period in which allergy appeared to have a protective effect was in the youngest adults surveyed–the 25- to 34-year-olds–where the risk odds ratio of having allergies and developing cancer was less than one–0.7.76

Immune function in cancer patients is sometimes tested by seeing whether they are capable of generating an allergic response. Both mainstream and some alternative medicines (notably the Gerson program) recognize the return of capacity for allergic response as evidence of a recovering immune system. Many alternative nutritional cancer therapies are widely reported to diminish allergic responses in healthy people, and for good reason: they often eliminate or greatly diminish exposure to common food allergens such as wheat, dairy products, caffeine, refined carbohydrates, chocolate, and eggs. That raises the question of whether or not there may be a benefit in reducing exposure to nutritional, chemical, or other allergic or hypersensitivity stresses in cancer. The hypothesis would be that relieving the significant immune stress of the allergy or hypersensitivity might support the recovery of immune potential to combat the cancer. I know of no research on this significant point.


So what can we conclude from the vitamin and mineral research? Certainly as much as this:

1. Vitamins A (with the retinoids and carotenoids), C, and E and several of the B vitamins have shown significant anticancer effects in experimental, epidemiological, and clinical studies. The most significant vitamins for general anticancer effect are the antioxidant vitamins A, C, and E. The use of these vitamins should be considered in both prevention and treatment.

2. Vitamin C has been the subject of a great controversy: it is not yet clear whether, in pharmacological doses, it enhances survival, as Cameron and Pauling claim. But more recent studies do indicate that it may have a protective effect against cancer, some antitumor effects, and the capacity to diminish side effects of radiotherapy and chemotherapy and improve outcomes. A few recent studies support Pauling and Cameron’s hypothesis that vitamin C may help slow tumor progression and extend life. Interesting cell line research proposes that vitamin C may be powerfully potentiated when administered in combination with vitamin K3.

3. Patients with leukemia should be cautious in taking vitamin C. One study shows that it enhanced leukemia development in some human leukemia cell lines and inhibited leukemia development in other cell lines. This raises the more important proposition that nutrients, in general, may act to enhance or inhibit cancer. This can be true not only in different cell lines or animal models, or in different human cancers, but the same nutrient may enhance or inhibit histologically identical cancers in different patients. However, this capacity of some nutrients to affect the same cancer in different directions is probably relatively rare, in comparison with the ability of specific nutrients to inhibit or enhance cancer unidirectionally.

4. Vitamin E has a wide range of positive effects in cancer–particularly vitamin E succinate. It enhances the effects of selenium, and enhances some chemotherapies, radiotherapy, and hyperthermia. It also may help prevent hair loss, and it protects the heart (in animal studies) from cardiac toxicity from doxorubicin.

5. B vitamin supplementation should be approached with care. Vitamin B12 can act both as a tumor promoter and a tumor-inhibitor; its tumor-enhancing activities are partially controlled by methionine. Vitamin B6 (pyridoxine) is deficient in many cancer patients and has been used to enhance the outcome of radiotherapy in a controlled prospective trial.

6. Among the minerals, selenium has broad immunopotentiating and anticancer effects, whereas zinc is a selenium antagonist. While zinc is an essential nutrient for life, great care should be taken in using zinc supplements with cancer.


1 Peter Greenwald, “Principles of Cancer Prevention: Diet and Nutrition.” In Vincent T. DeVita, Jr., ed., Cancer: Principles and Practice of Oncology (Philadelphia: J.B. Lippincott Company,1989), 169.

2 Ibid.

3 Ibid.

4 Ibid.

5 Ibid.

6 Ibid.

7 National Academy of Sciences, National Research Council, Committee on Diet, Nutrition and Cancer, Diet, Nutrition and Cancer (Washington, DC: National Academy Press, 1982), 9-5.

8 Greenwald, “Principles of Cancer Prevention: Diet and Nutrition.” In DeVita, ed., Cancer: Principles and Practice of Oncology, 170. See also Melvyn R. Werbach, Nutritional Influences on Illness (Tarzana, CA: Third Line Press, 1987), 103-4 and National Academy of Sciences, Diet, Nutrition and Cancer, 9-2-9-3.

9 M.S. Menkes et al., “Serum Beta-Carotene, Vitamins A and E, Selenium and the Risk of Lung Cancer,” New England Journal of Medicine 315:1250 (1986). Abstracted in Werbach, Nutritional Influences on Illness, 104.

10 L. LeMarchand, et al., “Vegetable Consumption and Lung Cancer Risk: A Population-Based Case-Control Study in Hawaii,” Journal of the National Cancer Institute 81(15):1158-64 (1989).

11 W.C. Willett, “Vitamin A and Lung Cancer,” Nutrition Review 48(5):201-11 (1990).

12 W. Bollag, “Vitamin A and the Retinoids: From Nutrition to Pharmacotherapy in Dermatology and Oncology,” Lancet 8329(1):860-3 (1983).

13 Waun Ki Hong et al., “13-Cis-Retinoic Acid in the Treatment of Oral Leukoplakia,” New England Journal of Medicine 315:1501-5 (1986).

14 William D. DeWys et al., “The Chemoprevention Program of the National Cancer Institute.” In Frank L. Meyskens, Jr. and Kedar N. Prasad, Vitamins and Cancer: Human Cancer Prevention by Vitamins and Micronutrients (Clifton, NJ: Humana, 1986), 301-10.

15 Lawrence Kushi, personal communication with the author, July 1990.

16 Frank L. Meyskens, Jr., “Prevention and Treatment of Cancer with Vitamin A and the Retinoids.” In K.N. Prasad, ed., Vitamins, Nutrition and Cancer (Basel: Karger, 1984), 266.

17 Ibid., 270.

18 Ibid., 271.

19 National Academy of Sciences, Diet, Nutrition and Cancer, 9-15.

20 Ibid., 9-12.

21 Ibid., 9-13.

22 M.E. Poydock et al., “Inhibiting Effect of Vitamins C and B12 on the Mitotic Activity of Ascites Tumors,” Experimental Cell Biology 47(3):210-7 (1979). Abstracted in Werbach, Nutritional Influences on Illness, 109.

23 Isao Eto and Carlos L. Krumdieck, “Role of Vitamin B12 and Folate Deficiencies in Carcinogenesis.” In Lionel A. Poirier et al., eds., Essential Nutrients in Carcinogenesis (New York: Plenum Press, 1986), 313-30.

24 Hans A. Ladner and Richard M. Salkeld, “Vitamin B6 Status in Cancer Patients: Effect of Tumor Site, Irradiation, Hormones and Chemotherapy.” In George Tryfiates and Kedar N. Prasad, eds., Nutrition, Growth and Cancer (New York: Alan R. Liss, 1988), 273-81.

25 Ibid., 278.

26 Robert D. Reynolds, “Vitamin B6 Deficiency and Carcinogenesis.” In Poirier, et al., eds., Essential Nutrients in Carcinogenesis, 339-45.

27 E. Cameron and L. Pauling, “Supplemental Ascorbate in the Supportive Treatment of Cancer: Prolongation of Survival Times in Terminal Human Cancer,” Proceedings of the National Academy of Sciences USA, 73:3685-9 (1976). See also “Supplemental Ascorbate in the Supportive Treatment of Cancer: Reevaluation of Prolongation of Survival Times in Terminal Human Cancer,” Proceedings of the National Academy of Sciences USA 75:4538-42 (1978). Both abstracts cited in Werbach, Nutritional Influences on Illness, 107-8.

28 E.T. Creagan et al., “Failure of High-Dose Vitamin C (Ascorbic Acid) Therapy to Benefit Patients with Advanced Cancer: A Controlled Trial,” New England Journal of Medicine 301:687-90 (1979). Ibid., 107.

29 C.G. Moertel et al., “High Dose Vitamin C versus Placebo in the Treatment of Patients with Advanced Cancer Who Have Had No Prior Chemotherapy: A Randomized Double-Blind Comparison,” New England Journal of Medicine 312:137-41 (1985). Ibid., 107.

30 Evelleen Richards, “Vitamin C Suffers a Dose of Politics,” New Scientist, 27 February 1986, 46-9.

31 Ibid., 48-9.

32 Maurice E. Shils, M.D., “Nutrition and Diet in Cancer.” In Maurice E. Shils and Vernon R. Young, eds., Modern Nutrition in Health and Disease (Philadelphia: Lea & Febiger, 1988), 1414.

33 Dietrich H. Hornig et al., “Ascorbic Acid.” In Shils and Young, Modern Nutrition in Health and Disease, 425. The citation of the Japanese hospital study was to A. Murata, F. Morishige, and H. Yamaguchi, “Prolongation of Survival Times of Terminal Cancer Patients by Administration of Large Doses of Ascorbate.” In A. Hanck, ed., Vitamin C: New Clinical Applications in Immunology, Lipid Metabolism and Cancer (Berne: Huber Verlag, 1982), 103-14.

34 National Academy of Sciences, Diet, Nutrition and Cancer, 9-8.

35 Gladys Block, “Epidemiologic Data on the Role of Ascorbic Acid in Cancer Prevention.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

36 Geoffrey Howe, “Dietary Factors and Risk of Breast Cancer: Combined Analysis of 12 Case-Controlled Studies,” Journal of the American Medical Association 82(7)561-9 (1990).

37 Richard I. Schwarz, “Ascorbate Stabilizes the Differentiated State and Reduces the Ability of Rous Sarcoma Virus to Replicate and to Uniformly Transform Cell Cultures.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

38 Alfred B. Hanck, “Vitamin C and Cancer.” In Tryfiates and Prasad, eds., Nutrition, Growth and Cancer, 307-20.

39 Ibid., 309.

40 Carmina Borek, “Free Radicals, Dietary Antioxidants and Mechanisms in Cancer Prevention: In Vitro Studies.” In Meyskens and Prasad, eds., Vitamins and Cancer, 68.

41 Ibid., 75.

42 Etsuo Niki, “Action of Ascorbic Acid as a Scavenger of Active and Stable Oxygen Radicals.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

43 Balz Frei and Bruce N. Ames, “Ascorbic Acid Protects Plasma Lipids Against Oxidative States.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

44 Joachim G. Liehr, “Inhibition by Vitamin C of Incidence and Severity of Renal Tumors Induced by Estradiol or Diethylstilbestrol.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

45 Hanck, “Vitamin C and Cancer.” In Tryfiates and Prasad, eds., Nutrition, Growth and Cancer, 310.

46 Vincenzo Noto et al., “Effects of Sodium Ascorbate (Vitamin C) and 2-Methyl-1,4-Naphthoquinone (Vitamin K3) Treatment on Human Tumor Cell Growth in Vitro,” Cancer 63:901-6 (1989).

47 Hanck, “Vitamin C and Cancer.” In Tryfiates and Prasad, eds., Nutrition, Growth and Cancer, 312.

48 Ibid., 312-4.

49 Paul Okunieff, “Interactions Between Ascorbic Acid, Radiation Therapy, and Misonidazole.” Meeting abstract, Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

50 Kan Shimpo et al. “Ascorbic Acid and Adriamycin Toxicity.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

51 K.N. Prasad et al., “Sodium Ascorbate Potentiates the Growth Inhibitory Effect of Certain Agents on Neuroblastoma Cells in Culture,” Proceedings of the National Academy of Sciences USA 76(2):29-32 (1979). See also K.N. Prasad, “Modulation of the Effects of Tumor Therapeutic Agents by Vitamin C,” Life Sciences 21(2):275-80 (1980). Abstracts cited in Werbach, Nutritional Influences on Illness, 108.

52 Chan H. Park, “Vitamin C in Leukemia and Preleukemia Cell Growth.” In Tryfiates and Prasad, eds., Nutrition, Growth and Cancer, 321-30.

53 Chan H. Park and Bruce F. Kimler, “Growth Modulation of Human Leukemic and Preleukemic Progenitor Cells by L-Ascorbic Acid.” Meeting abstract, “Ascorbic Acid: Biological Functions and Relation to Cancer,” National Institutes of Health, Bethesda, MD, 10-2 September 1990.

54 National Academy of Sciences, Diet, Nutrition and Cancer, 9-10.

55 Ibid.

56 Kedar N. Prasad, “Summary and Overview.” In Poirier et al., eds., Essential Nutrients in Carcinogenesis, 543-7.

57 K.N. Prasad, “Mechanisms of Action of Vitamin E on Mammalian Tumor Cells in Culture.” In Tryfiates and Prasad, eds., Nutrition, Growth and Cancer, 363-75.

58 Ibid., 364.

59 K.N. Prasad, “Modification of the Effect of Pharmacological Agents, Ionizing Radiation and Hyperthermia on Tumor Cells by Vitamin E.” In Prasad, ed., Vitamins, Nutrition and Cancer, 76-104.

60 K.N. Prasad et al., “Vitamin E Enhances the Growth Inhibitory and Differentiating Effects of Tumor Therapeutic Agents on Neuroblastoma and Glioma Cells in Culture,” Proceeds of the Society for Experimental Biological Medicine 164(2):158-63 (1980). Abstracted in Werbach, Nutritional Influences on Illness, 109-10.

61 L. Wood, “Possible Prevention of Adriamiacin-Induced Alopecia by Tocopherol,” New England Journal of Medicine 312:1060 (1985). Abstract cited in Werbach, ibid.

62 K.N. Prasad, Vitamins Against Cancer: Fact and Fiction (Denver: Nutrition Publishing House, 1984), 91.

63 Ibid., 65-7.

64 Gerhard N. Schrauzer, “Selenium in Nutritional Cancer Prophylaxis.” In K.N. Prasad, ed., Vitamins, Nutrition and Cancer, 240-50.

65 Ibid., 243.

66 Ibid., 244.

67 Ibid., 243.

68 Carmia Borek, “Free Radicals, Dietary Antioxidants and Mechanisms in Cancer Prevention: In Vitro Studies.” In Meyskens and Prasad, eds., Vitamins and Cancer, 65-92.

69 Ibid., 73.

70 National Academy of Sciences, Diet, Nutrition and Cancer, 10-8.

71 Ibid., 10-8-9.

72 Ibid., 10-10-11.

73 William P. McWhorter, “Allergy and Risk of Cancer: A Prospective Study Using NHANESI [First National Health and Nutrition Examination Survey] Followup Data,” Cancer 62:451-5 (1988).

74 Ibid., 454.

75 Maurice E. Shils, “Nutrition and Neoplasia.” In Robert S. Goodhart, M.D., and Maurice E. Shils, M.D., eds., Modern Nutrition in Health and Disease (Philadelphia: Lea & Febiger, 1980), 1177.

76 McWhorter, “Allergy and Risk of Cancer,” 453.