iThyroid.com

CANCER

Following is an interesting study which shows a couple things. First, seafood consumption and shellfish in particular, is a protector against thyroid cancer. My guess is that this is the result of getting more ultratrace minerals. Of greater interest is the fact that long-term use of multivitamins increases thyroid cancer risk. I suspect that this is due to the depletion of trace minerals by zinc, iron, and other normal metals found in these supplements. I am working on a hypothesis that the trace mineral that is depleted that is most important in thyroid cancer is cadmium. Cadmium seems to be important in immune system function for killing tumor cells.

 

Ann Epidemiol 2002 Aug;12(6):395-401

Lifestyle and other risk factors for thyroid cancer in Los Angeles County females.

Mack WJ, Preston-Martin S, Bernstein L, Qian D.

University of Southern California, Department of Preventive Medicine, Los Angeles, CA 90089, USA.

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15-54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980-81 and 147 diagnosed in 1982-83). Female neighborhood controls (n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1-3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05-0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2-7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

 

Cancer Epidemiol Biomarkers Prev 2001 Sep;10(9):979-85

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Horn-Ross PL, Morris JS, Lee M, West DW, Whittemore AS, McDougall IR, Nowels K, Stewart SL, Spate VL, Shiau AC, Krone MR.

Northern California Cancer Center, Union City, California 94587, USA. phornros@nccc.org

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Title
            Dietary iodine deficiency as a tumor promoter and carcinogen in male F344/NCr rats.
Author
            Ohshima M; Ward JM
Source
            Cancer Res, 46(2):877-83 1986 Feb
Abstract

 

Adv Exp Med Biol 1999;472:29-42

t

Nutritional factors in human cancers.

Giovannucci E

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

A variety of external factors interacting with genetic susceptibility influence the carcinogenesis process. External factors including oxidative compounds, electrophilic agents, and chronic infections may enhance genetic damage. In addition, various hormonal factors which influence growth and differentiation are critically important in the carcinogenic process. Diet and nutrition can influence these processes directly in the gastrointestinal tract by providing bioactive compounds to specific tissues via the circulatory system, or by modulating hormone levels. Differences in certain dietary patterns among populations explain a substantial proportion of cancers of the colon, prostate and breast. These malignancies are largely influenced by a combination of factors related to diet and nutrition. Their causes are multifactorial and complex, but a major influence is the widespread availability of energy-dense, highly processed and refined foods that are also deplete in fiber. These dietary patterns in combination with physical inactivity contribute to obesity and metabolic consequences such as increased levels of IGF-1, insulin, estrogen, and possibly testosterone. These hormones tend to promote cellular growth. For prostate cancer, epidemiologic studies consistently show a positive association with high consumption of milk, dairy products, and meats. These dietary factors tend to decrease 1.25(OH)2 vitamin D, a cell differentiator, and low levels of this hormone may enhance prostate carcinogenesis. While the nutritional modulation of growth-enhancing and differentiating hormones is likely to contribute to the high prevalence of breast, colorectal, prostate, and several other cancers in the Western world, these cancers are relatively rare in less economically developed countries, where malignancies of the upper gastrointestinal tract are quite common. The major causes of upper gastrointestinal tract cancers are likely related to various food practices or preservation methods other than refrigeration, which increase mucosal exposure to irritants or carcinogens.

Risk factors of thyroid cancer among women in Tokai, Japan.

Takezaki T, Hirose K, Inoue M, Hamajima N, Kuroishi T, Nakamura S, Koshikawa T, Matsuura H, Tajima K

Soy, tea, and cancer benefits
From: Science News, April 29, 2000

Soy-rich diets appear to help fight certain cancers. Tea drinking has been linked to similar benefits. Two studies now find that the combo offers a potent double whammy against cancer of the breast and prostate-at least in mice.

Jin-Rong Zhou and his colleagues at Harvard Medical School in Boston injected a million breast cancer or prostate cancer cells into mice engineered to possess weak immune systems. Two weeks earlier, they had replaced the drinking water of some animals with green or black tea. Others received chow laced with isoflavones, soy's biologically active antioxidants. Two groups of mice got both the mix of isoflavones and one or the other tea. Some just ate their normal diet.

Two months after implantation of the cancer cells, the researchers surveyed for tumors and found that all the experimental diets had conferred some benefit. Compared with animals on the normal diet, mice given isoflavones or tea had 25 to 50 percent fewer tumors, and their tumors weighed 15 to 25 percent less. However, benefits from pairing tea and isoflavones equaled or exceeded the sum of either alone--a reduction of between 72 and 87.5 percent in tumor number and a similarly large decrease in each tumor's size. -JR.

Hormones And Breast Cancer 

Some hormone replacement may give women more than they bargained 
for. A study published in the journal Cancer finds that a 
combination estrogen-progestin therapy may more than double the 
risk of a kind of breast cancer in some women. Researchers from 
the Fred Hutchinson Cancer Research Center in Seattle looked at 
537 women aged 50 or older who had breast cancer from 1988 to 
1990 and 492 women who did not have the disease. They found that 
those women who had taken combination hormone replacement for at 
least six months had a 2.6 times higher incidence of lobular 
breast cancer (cancer of the milk-producing lobules of the 
breast) compared to women who had not taken hormone replacement. 
Most of the women in the study who took hormone replacement had 
taken it for an average of four years. The researchers say more 
study is needed to confirm their results and determine whether 
some women may have characteristics that make them more 
susceptible to this form of breast cancer. Their findings come 
following earlier studies that also suggest an increased risk of 
breast cancer from combination hormone replacement therapy, but 
not from estrogen-only therapy, The Associated Press reports. 
Studies also have suggested that cases of lobular breast cancer 
are on the rise in the United States, the AP says.

Women With Thyroid Cancer at Increased Risk for Breast Cancer
by Mary J. Shomon  9-29-00

According to a retrospective study conducted at the University of Texas MD Anderson Cancer Center, younger women with thyroid cancer have an increased risk of developing breast cancer later in life. The study establishes a relationship between the post-surgical use of radioactive iodine (RAI) I31I treatments for thyroid cancer, and later development of breast cancer.

The authors of the study, "The Development of Breast Cancer in Women with Thyroid Cancer," are all from the The University of Texas MD Anderson Cancer Center Houston, TX. Their findings are being presented at the annual meeting of the American Academy of Otolaryngology--Head and Neck Surgery Foundation Annual Meeting in Washington, D.C.

Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, the researchers found that young women (30-34 years) with thyroid cancer exhibited the greatest risk of developing breast cancer. Women who were between the ages of 40 and 44 at initial diagnosis of thyroid cancer were also at significantly elevated risk. The data suggested that the greatest risk appears 15-20 years after the thyroid cancer.

The study concluded that premenopausal adult Caucasian women who are treated for differentiated thyroid cancer are at increased risk to develop breast cancer five to 20 years later. Breast cancer, however, does not increase the risk of subsequent thyroid cancer. This finding suggests that the increased risk of breast cancer after thyroid cancer is related to the thyroid cancer treatment. In particular, the RAI treatment is suspected to be the agent involved in increasing the cancer risk.

The authors' recommendation is for regular follow-up of all women patients with thyroid cancer and "judicious use of radioactive iodine as a treatment regimen."

Important Issues for Thyroid Patients

If you are a female thyroid cancer patient, or Graves'/hyperthyroidism patient who has undergone RAI, you should pay particular attention to preventive factors for breast cancer, including diet, exercise, and healthy body weight. You should incorporate some form of regular screening - i.e., monthly breast self-exams, regular professional breast examinations, and/or mammograms - into your health care.

Another key question that this important finding raises is whether or not the use of RAI to treat hyperthyroidism and Graves' disease puts women at an equally increased risk of breast cancer. Given that researchers are suggesting that the RAI is the factor that is the likely cause of the subsequent breast cancer, this is a critical question that must be examined soon, for the sake of Graves' and hyperthyroidism patients. RAI is the most common treatment recommended for hyperthyroidism and Graves' disease in the United States, but less common in Europe, where surgery is typically preferred.

The following study may offer some clues about the nutrient relationships that lead to breast cancer. However, it will probably take time to see how this fits in with other information.

 

Rev Environ Health 2000 Jul-Sep;15(3):337-58

Association between malignant tumors of the thyroid gland and exposure to environmental protective and risk factors.

Frentzel-Beyme R, Helmert U.

Department for Environmental and Occupational Epidemiology, Bremen Institute for Prevention Research and Social Medicine, Germany. beyme@bips.uni-bremen.de

Risk factors for thyroid carcinomas and adenomas were investigated using a standard questionnaire in a case-control study in Southwestern Germany, a known iodine deficiency area. A clinical registry, set up after the Chernobyl accident at the University hospital Mannheim, served as the basis for 174 incident cases of each diagnostic group. Interview data were compared within and with prevalences from a population-based matched control group of equal size from the entire area. The protective role of coffee drinking and the consumption of cruciferous vegetables, such as broccoli, were confirmed for both genders. A high consumption of tomatoes (> 200/year) was associated with an elevated risk of > 2.5 for malignant tumors but not for benign tumors in both genders. In both genders, both treatment for goiter (hyperthyroidism) and decaffeinated coffee consumption were associated with an increased risk for malignant tumors, but less so for adenomas. In women, early menarche (< 13 years) and stillbirth after first pregnancy, as well as hysterectomy, were substantial risk factors. Occupational variables and radiation, including medical indications and mammography, did not reveal particular risks. We did not address the role of regular iodine substitution, but did analyze the consumption of freshwater fish and seafood. Multivariate analyses of the most prominent risk factors confirmed the persistence of tomato consumption as a risk factor. In view of experimental evidence on the carcinogenicity of organophosphates and the neurotoxicant effect of certain agrochemicals on neuroendocrinologically regulated organs, we postulate that in Germany, importing off-season tomatoes from areas with a known history of possible inexperienced use of agrochemicals may be associated with a promoting effect for malignant neoplasias of the thyroid gland in terms of promoting already existent proliferating tissue growth.

 

Adv Clin Path 2000 Jan;4(1):11-7

Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach.

Venturi S, Donati FM, Venturi A, Venturi M, Grossi L, Guidi A.

Servizio di Igiene, Regione Marche, 1-61016-Pennabilli, Italy. venturis@nf.infotel.it.

The authors have hypothesized that dietary iodine (deficiency or excess) is associated with the development of some gastric and mammary cancers, as it is well-known for thyroid cancer. They report a short review of their own work and of the general literature on this correlation and on the antioxidant function of iodide in stomach, breast and thyroid. Thyroid cells phylogenetically derived from primitive iodide-concentrating gastroenteric cells which, during evolution, migrated and specialized in uptake and storage of iodine, also in order to adapt the organisms from iodine-rich sea to iodine-deficient land. Mammary cells also derived from primitive iodide-concentrating ectoderm. Stomach, breast and thyroid share an important iodide-concentrating ability and an efficient peroxidase activity, which transfers electrons from iodides to the oxygen of hydrogen peroxide and so protects the cells from damage caused by lipid peroxidation. The authors suggest that iodide might have an ancestral antioxidant function in all iodide-concentrating cells from primitive Algae to more recent Vertebrates. In Italy, gastric cancer is more frequent in farmers and in iodine-deficient populations, living in mountainous and hilly areas, than in fishermen. In the last two decades, Italian decrease of gastric cancer seems to be correlated more to the higher dietary consumption of iodine-rich fish rather than to consumption of fruit and vegetables, which indeed has decreased in Italy.

 

 

J Clin Endocrinol Metab 2000 Apr;85(4):1513-7

The changing incidence and spectrum of thyroid carcinoma in Tasmania (1978-1998) during a transition from iodine sufficiency to iodine deficiency.

Burgess JR, Dwyer T, McArdle K, Tucker P, Shugg D.

Department of Diabetes and Endocrine Services, Royal Hobart Hospital, Australia. jburges@postoffice.utas.edu.au

Exposure to ionizing radiation, changing levels of iodine nutrition, and increased pathologic diagnosis of clinically unimportant thyroid neoplasia have all been proposed as explanations for a worldwide rise in the incidence of thyroid carcinoma (TC) over the past 6 decades. Tasmania is geographically an area of endemic iodine deficiency. In this report, we describe the spectrum of TC in a population averaging 450,000 persons during a 21-yr period that spans the communities transition from iodine sufficiency to iodine deficiency after discontinuation of universal iodine prophylaxis in the mid 1980s. The Tasmanian Cancer Register was used to ascertain all cases of TC diagnosed in Tasmania between 1978 and 1998. Histopathological and demographic data were reviewed. A total of 289 cases of TC were identified. Papillary TC (PTC), follicular TC, medullary TC, and other species accounted for 62%, 23%, 4%, and 11% of cases, respectively. The age standardized incidence rate for total TC increased from 2.45 to 5.33 per 100,000 for females and 0.75 to 1.76 per 100,000 for males between 1978 and 1984 and 1992 and 1998, respectively. A rise in the incidence of PTC by 4.5-fold (P < 0.05) in females and 2.1-fold in males (not significant) was the dominant change over this period. In parallel, the proportion of follicular TC relative to PTC fell from 0.35 to 0.17 during these years (P < 0.05). The rise in PTC incidence was, in part, due to an increase in the occurrence of tumors 1cm or less in diameter. Nonetheless, a 3-fold rise in incidence of larger lesions was also observed during the study period. Forty-three (24%) PTC cases had multifocal disease, 17 (40%) of whom had bilateral tumors. Familial (autosomal dominant) PTC was identified in nine (5%) total PTC cases. Prior studies have linked iodine prophylaxis to a rise in the proportion of differentiated TC, particularly PTC. Our data suggest a complex relationship between iodine nutrition and thyroid tumorigenesis. Factors such as a long latency between changes in iodine nutrition and thyroid tumorigenesis, a dose threshold for the effect of iodine nutrition on thyroid tumorigenesis, and an interaction between iodine nutrition and thyroidal sensitivity to ionizing radiation may all play a role.

PROSTATE CANCER

Email from the wife of a man with prostate cancer:

Yesterday we went to Lahey Clinic and my husband had all kinds of tests.  They said
he was deficient in magnesium and he had another hormone shot.  He has lost
20 pounds is tired all the time and looks swollen and coloring is on the
yellowish side.  They are supposed to put the radiation seeds in September.
I'm worried as he looks worse since the treatments began than he did before.

What does it mean to be low in magnesium?

John:

Generally low magnesium is the result of low copper. Copper works with magnesium while zinc (the partner of copper) works with calcium (the partner of magnesium). Basically if magnesium is low, copper is relatively low, calcium and zinc are relatively high.

Low copper will cause an increase in heart rate, panic attacks, and the loss of weight from an increase in thyroid hormones. Solgar makes a 2.5 mg. copper supplement and it sounds like it would be a good idea for Jim to take 2 to 4 of these a day. 
One cause of a yellowish coloring is low T3 (the thyroid hormone that the cells use). What happens is that the conversion of beta carotene is driven by T3, so this conversion decreases and the beta carotene builds up in the skin. 

Generally this yellowish coloring indicates that T4 (the hormone the thyroid gland makes) isn't being converted to T3 (the hormone the cells use). This T4 to T3 conversion requires a deiodinase enzyme which cuts one of the four iodine atoms off the T4 to make the T3 which has three iodine atoms.

This deiodinase enzyme contains the element selenium, so having adequate selenium in the body is an absolute necessity for converting T4 to T3. Low selenium is also the primary cause of prostate cancer. What is happening in prostate cancer is that the deficiency of selenium causes the prostate to enlarge so that it can filter more blood to get the scarce selenium that it needs.

While doctors think that this enlargement is something to destroy with radiation or surgery, I consider this enlargement the body's attempt to deal with the selenium deficiency. The correct strategy is to provide selenium to the body in the form of a supplement so that the prostate can resume normal functions and reabsorb the excess tissue that it has built up. Generally 400 mcg of a yeast-based selenium is a good supplemental amount, but if I were in that situation I'd take more, perhaps up to 800-1000 mcg per day until the situation resolved. Toxicity for selenium typically begins at 1400 mcg daily for an extended period, and the body may be able to tolerate more without toxic effects if there is good availability of the other nutrients that work with selenium, such as vitamin E (400-800 IU per day is good) and copper.

While radiation, drugs, and surgery are the current medical treatments for prostate cancer, it is my strong belief that cancer is a nutritional deficiency disease and that these treatments are entirely inappropriate and damaging. Standard medical treatment will severely damage the health of the person and does nothing to correct the real problem, which is starvation of essential nutrients. Everyone would laugh if radiation, drugs, and surgery were the standard treatments for scurvy, which is a vitamin C deficiency disease, and that is exactly what people in the future will do when they look back at how the medical professionals of the 21st century were so incredibly ignorant about the nutritional deficiencies which cause cancer.

Hormone Replacement Therapy Linked to Breast Cancer

Adding to evidence that hormone replacement therapy (HRT) can potentially raise a woman's risk of breast cancer, a new US study links recent, long-term HRT with a heightened risk of the disease.

Researchers found that HRT with estrogen alone or estrogen-plus-progestin was associated with a 70% increase in breast cancer risk when the therapy was taken for 5 years within the 6 years preceding the cancer diagnosis.

The findings build on previous research showing a link between long-term HRT and breast cancer and help clear up the question of whether combination HRT and estrogen-only HRT carry similar risks.

In addition, the study of about 1,300 women found that HRT use had a particular link to lobular breast cancer, the form of the disease that begins in the breast's lobules. It is far less common than ductal breast cancer, which begins in the milk ducts.

Women who were recent, long-time users of HRT faced a three-fold risk of lobular cancer compared with women who never used HRT.

These women also had about a 50% increase in the risk of ductal cancer.

JAMA February 13, 2002;287:734-741

DR. MERCOLA'S COMMENT:

After all these years of estrogen hype it is becoming more and more clear to traditional medicine that the benefits of estrogen don't outweigh the risks.

Estrogen has long been proven to not help with heart disease nor prevent Alzheimer's.

So that leaves us with osteoporosis and hot flash relief.

It has been my experience that black cohosh works far more effectively for hot flash relief.

So that leaves us with osteoporosis. Well, a study published less than a year ago in JAMA showed that estrogen was not helpful to prevent against hip fractures.

Fortunately one can take vitamin D, K, omega three fats and plenty of vegetables and exercise to address osteoporosis.

One can only logically conclude that there is no reason for a woman to take hormone replacement therapy, unless her ovaries have been removed or she is interested in getting breast cancer.

It is important to make a distinction between women who have had their ovaries removed and those that have not. Those that have will likely benefit from low dose natural human estrogen replacement while those who still have ovaries will likely not.

The following article suggests that cancer might be caused by deficiencies of certain metals.

 

Eur J Clin Pharmacol 1994;47(1):1-16

Complexes of metals other than platinum as antitumour agents.

Kopf-Maier P.

Institut fur Anatomie, Freie Universitat Berlin, Germany.

The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

Cancer nutrition information
    Great info (JJ)

http://www.healthy.net/library/articles/quillin/technica.asp

© 1994 Patrick Quillin, Ph.D., R.D.

This chapter is provided for the person who enjoys knowing more of the intimate details on how nutrition interrupts the cancer process. This section is to be considered more exemplary rather than comprehensive. If I included all the data in this field, then this book would be unwieldy. These references provide a scientific foothold upon which to recommend nutrition therapy in conjunction with traditional oncology care. For more information, see:

Books:

Non-Technical

CANCER THERAPY, by Ralph Moss, PhD
CANCER AND ITS NUTRITIONAL THERAPIES, by Richard Passwater, PhD
BEATING THE ODDS, by Albert Marchetti, MD
WHAT YOUR DOCTOR WON'T TELL YOU, by Jane Heimlich
VITAMINS AGAINST CANCER, by Kedar Prasad, PhD
HOW TO FIGHT CANCER AND WIN, by William Fischer

Technical

ADJUVANT NUTRITION IN CANCER TREATMENT, by Patrick Quillin, PhD,RD
VITAMINS AND CANCER by Frank Meyskens, MD
VITAMINS AND MINERALS IN THE PREVENTION AND TREATMENT OF CANCER by Maryce Jacobs, PhD
MODULATION AND MEDIATION OF CANCER BY VITAMINS, by Frank Meyskens, MD
ESSENTIAL NUTRIENTS IN CARCINOGENESIS, by Lionel Poirier

Purpose of Using Adjuvant
Nutrition in Cancer Treatment

1. Preventing malnutrition. Cancer is a serious wasting disease, elevating basal metabolism, altering bio-energetics, and oftentimes inducing anorexia. The net effect is that 40% or more of cancer patients actually die from malnutrition, not from the cancer.¹ The American College of Physicians issued a position paper in 1989 stating:"...the evidence suggests that parenteral nutritional support [in cancer treatment] was associated with net harm, and no conditions could be defined in which such treatment appeared to be of benefit."² This "meta-analysis" of the literature specifically excluded cancer patients who were malnourished. Nutrition support is meant to relieve malnutrition, not cure cancer. Extensive chemotherapy or radiation therapy are, in themselves, sufficient stressors to induce catabolic malnutrition.³ Additionally, standard Intensive Care Unit parenteral formulas may be inappropriate for cancer patients since high glucose solutions may feed tumor growth.

2. Bolstering immune functions. From textbooks⁴ to extensive reviews of the literature⁵, it has been clearly demonstrated that a strong link exists between nutrient intake and the quality and quantity of human immune factors. Researchers provided 30 milligrams of beta carotene (or 50,000 iu, which is 10 times the Recommended Dietary Allowance of vitamin A), to healthy older adult volunteers with a dose dependent increase in natural killer cell activity (NK) and interleukin-2 receptors.⁶ Similar results have been found with vitamin E, B-6, C, and zinc.

3. Nutrients as biological response modifiers.

Immune modulation

cleave immune complexes: i.e. proteolytic enzymes

improve quantity: via precursors for immune cytotoxic activity, nitric oxide from arginine for enhanced chemotaxis; increase NK, TNF, total lymphocytes via beta carotene, vitamin A, C, E, B-6 etc.

improve quality: via increase in tumor recognition using enzymes or emulsified vitamin A

reduce antigens: via oligoantigenic diet

thymotropic: via arginine supplements and thymus gland extract

immune sparing: antioxidants that lower turnover in cell mediated immunity or an increase in circulation of immune factors, i.e. vitamin E protects lymphocytes from oxidative damage in chemotaxis

Alter genetic expression

down regulate oncogene: i.e. soybean protease inhibitors alter c-myc oncogene

genetic repair: increase DNA polymerase activity and decrease in base pair fragility via zinc & folate

inhibit episome production: via vitamin D

directly affect gene receptors: i.e. vit. A

Alter cell membrane dynamics

K to Na ratio: may alter membrane permeability & thus flow of oxygen & nutrients into & out of cell (an anaerobic environment is more conducive to tumor cell mitosis)

dietary fat intake: affects lipid bi-layer content in cell membrane, thus membrane dynamics & oxygenation

prostaglandin metabolism: macronutrients influence hormones which influence prostaglandin branch points, which can affect aggregation and adhesiveness of cell membranes, thus metastatic potential of tumor

Influence detoxification

urinary output: fluid intake & diuretics (e.g. coffee & alcohol)

fecal excretion: fluid and fiber intake coupled with nutrients that encourage peristalsis

cytochrome P450

endogenous biosynthesis of detoxification enzymes: catalase, SOD, GSH through selenium and vitamin E

immune stimulation: encourages detox

low temperature saunas encourage excretion of toxins via skin pores

respiratory quotient indicates efficiency of oxidative respiration, which can be retarded by heavy metal toxicity

Alter acid/base balance

all foods influence pH. Tumor cells thrive in acidosis.

alkalizing diet (high in most plant food items) encourages detox of heavy metals

Cell/cell communication

gap cell junctions for ionic communication between cells and nucleus, i.e. vitamin A may be able to revert abnormal DNA back to normal DNA (prodifferentiation or cytodifferentiation) and cell content via gap cell junction

Prostaglandin synthesis

affected by macronutrient intake and serum insulin levels

immune modulation: PGE-1 vs PGE-2, via eicosapentaenoic acid or gamma linolenic acid

membrane aggregability and metastasis are heavily influenced by prostaglandin metabolism

estrogen binders: PGE-1 increases endogenous biosynthesis of circulating estrogen receptors, PGE-1 probably also helps with androgen-driven prostatic cancer

Affect steroid hormone activity

fat from diet and body influence estrogen output

phytoestrogens in diet (i.e. soybeans): may retard hormone-driven cancer lignans (from plant food) can provide estrogen binders or analogs to educe estrogen activation of tumors

Alter polyamine synthesis

polyamines can accelerate cancer growth, while B-6 creates polyamine complexes and accelerates their excretion

Bioenergetics

selective starve tumors by:

depriving anaerobic and fermenting tumors of their preferential substrate, glucose

altering mitochondrial membranes of tumor, such as with Vitamin C

employ nutrients that encourage aerobic metabolism: CoQ, chromium, niacin, riboflavin, polyunsaturated fats, exercise

Pro & antioxidants

therapeutic levels of antioxidants: protect healthy tissue from free radical destruction of chemotherapy & radiation therapy.(i.e. vitamin E, C, beta-carotene, selenium)

certain form and dose of pro-oxidants (i.e. non-heme iron): can accelerate tissue destruction and is sequestered by tumor & pathogens

Anti-proliferative agents

selective toxins for anti-neoplastic activity: i.e. garlic and other minor dietary constituents in plant food

homeostatic mechanism for down regulation of growth: possible role for selenium

anti-angiogenesis factor (hyaluronic acid or other proteins in cartilage, ie. shark cartilage and bovine tracchea)

Influence cell differentiation

retinoids, vitamin D, enzymes

The Protective Action of Vitamins
Against Cancer Include:⁷

• preventing the formation of carcinogens
• increasing detoxification
• inhibiting transformed cell replication
• controlling expression of malignancy
• controlling differentiation processes
• enhancing cell to cell communication

A Sampling of Cancer Antagonists Found in Varoius Foods (With Active Ingredient in Parentheses)⁸

inhibitors of covalent DNA binding

broccoli & cabbage (phenethyl isothiocyanate)
fruits, nuts, berries, seeds, and vegetables (ellagic acid)
fruits & vegetables (flavonoids in polyphenolic acid)

inhibitors of tumor promotion

orange & yellow fruits & vegetables (retinol)
nuts & wheat germ (vitamin E)
fruits & vegetables (vitamin C)
green, orange, & yellow fruits and vegetables (beta-carotene)
garlic & onions (organosulfur compounds, reduce the formation of organosoluble metabolites and increase the formation of water soluble metabolites which are easier to excrete)
curry/tumeric (curcumin)
chili peppers (capsaicin, a vanillyl alkaloid)

inducing biotransformation

cabbage, brussel sprouts, spinach, cauliflower and broccoli (indole-3-carbinol)
seafood & garlic (selenium)

reducing the absorption of carcinogens

fruits, vegetables, grains & nuts (fiber)
fruits & vegetables (riboflavin chlorophyllin)

Nutrients can Reverse Pre-Malignant Lesions

Vitamin C and beta-carotene are effective at reversing cervical dysplasia and oral leukoplakia in humans.⁹

Vitamin A derivatives (retinoids) reverse bronchial metaplasia in humans.¹⁰

Combination of folate and vitamin B-12 reversed bronchial metaplasia in humans.¹¹

Injections of vitamin E, beta-carotene, canthaxanthin (a carotenoid) and algae extract dramatically bolstered levels of tumor necrosis factor alpha and reversed hamster buccal pouch tumors.¹²

58 adults with familial adenomatous polyps (near 100% progression to cancer if untreated) were entered into a randomized study providing high dose vitamin C with E and high fiber, or placebo plus low fiber diet. The high fiber group experienced a limited degree of polyp regression.¹³

Nutrients can Inhibit Carcinogenesis

Beta-carotene, vitamin A, C, E reduce the risk of cancer by radiation and chemical carcinogen exposure. Vitamins A, D, and E inhibit the expression of oncogenes.¹⁴

Calcium supplements (2000 mg/day) provided a marked suppression of rectal proliferation in experimental but not placebo patients. Calcium seems to markedly inhibit the early stages of colon cancer in genetically vulnerable individuals.¹⁵

Taking vitamin supplements was protective against colo-rectal cancer in a large Australian study.¹⁶

The former medical director of Sloan Kettering cancer hospital in New York (Robert Good, MD, DSc) has found that many nutrients modulate immune functions and can protect against cancer.¹⁷

An extensive book by a former National Cancer Institute oncologist, Dr. Charles Simone, shows the potency of nutrients to prevent cancer.¹⁸

Professors at Harvard University have published considerable evidence in the prestigious New England Journal of Medicine showing that 90% of all cancer is environmentally caused and therefore preventable. They cite our 500% higher incidence of breast cancer as being related to diet. They highlight fat, selenium, vitamin A, C, E, and fiber and prime proven nutrition cancer preventers.¹⁹

Common Malnutrition in Cancer Patients (and Intervention with Total Parenteral Nutrition, TPN)

A theory has persisted for decades that one could starve the tumor out of the host. Unfortunately, the tumor is quite resistant to starvation. Most studies find more harm to the host than the tumor in either selective or blanket nutrient deficiencies.²³ Protein restriction does not affect the composition or growth rate of the tumor, but does restrict host growth rate.²⁴ Folate deprivation allowed the tumor to grow anyway.²⁵ In starved animals, the tumors grew more rapidly than in fed animals, indicating the parasitic tenacity of tumors in the host.²⁶ In animal studies, starving the host led to continued tumor growth and wasting of host tissue.²⁷ Overall, the research shows that starvation provokes host wasting while tumor growth continues unabated.²⁸ Pure malnutrition (cachexia) is responsible for at least 22% and up to 67% of all cancer deaths. While the average "healthy" American is sub-clinically malnourished, the average cancer patient is clinically malnourished. Malnutrition is extremely common in the cancer patient.

Of the 139 lung cancer patients studied, most tested deficient in vitamin C or scorbutic (clinical vitamin C deficiency).²⁹

Another study of cancer patients found that 46% tested scorbutic while 76% were below acceptable levels for serum ascorbate.³⁰

Experts now recommend the value of nutritional supplements, especially in patients who require prolonged TPN support.³¹

Interleukin-2 therapy induced malnutrition in up to 90% of 20 patients tested. The authors recommend prophylactic nutritional supplements to stem the immune suppression from this iatrogenic malnutrition.³²

Recommended Dietary Allowances (RDA) are not designed for cancer patients. Supplements of vitamins, minerals, and other nutrients can benefit the cancer patients.³³

Progressive weight loss is common in cancer patients and is a major source of morbidity and mortality.³⁴

Wasting of tissue occurs in hypermetabolic states, most commonly for injury patients and end-stage cancer.³⁵

Chemo and radiation therapy are sufficient stressors in themselves to induce malnutrition.³⁶

Up to 80% of all cancer patients have reduced levels of serum albumin (a leading indicator of protein/calorie malnutrition).³⁷

There is some evidence that tumors are not as flexible in using substrates other than glucose for fuel, hence a low carbohydrate TPN formula may have antineoplastic value.³⁸ A recently published position paper from the American College of Physicians basically stated that TPN had no effect on the outcome of cancer patients.³⁹ Unfortunately, this article selected non-malnourished patients. TPN treats malnutrition, not cancer.⁴⁰

Weight loss drastically increases the mortality rate for most types of cancer, while also lowering the response to chemotherapy.⁴¹

TPN improves tolerance to chemotherapeutic agents and immune responses.⁴² Of 28 children with advanced malignant disease, 18 received TPN for 28 days with resultant improvements in weight gain, increased serum albumin, and transferrin with major immunological benefits. In comparing cancer patients on TPN versus those trying to nourish themselves by oral intake of food, TPN provided major improvements in calorie, protein, and nutrient intake but did not encourage tumor growth.

27 malnourished cancer patients were provide TPN and had a mortality rate of 11%, while the non-TPN group had a 100% mortality rate.⁴³

Pre-operative TPN in patients undergoing surgery for GI cancer provided general reduction in the incidence of wound infection, pneumonia, major complications, and mortality.⁴⁴

In one study by Mullen, the patients who were the most malnourished experienced a 33% mortality and 46% morbidity rate, while those least malnourished had a 3% mortality rate with an 8% morbidity rate.

There is evidence that a finely tuned TPN formula can do more than just nourish the patient with broad spectrum nutrient coverage. TPN formulas fortified with arginine have been shown to stimulate the immune system, accelerate wound repair, and promote tumor reduction. Modified diets with low tyrosine (2.4 mg/kg body wt) and low phenylalanine (3.5 mg/kg body wt) were able to elevate natural killer cell activity in 6 of 9 subjects tested.⁴⁵

In 21 adults on TPN, high amino acid solution (designed for pediatric ICU) with 30% branched chain amino acids was able to provide better nitrogen balance than the conventional 8.5% amino acid TPN formula.⁴⁶

In 20 adult hospitalized patients on TPN, the mean daily needs (based on urine and serum ascorbate levels) for vitamin C were 975 mg with the range being 350-2250 mg.⁴⁷

49 patients with small cell bronchogenic carcinoma received chemotherapy with (21 patients) or without (28 patients) TPN. Complete remission was achieved in 85% of the TPN group versus 59% of the non-TPN group.⁴⁸

In an extensive study of 3,047 cancer patients through the Eastern Cooperative Oncology Group, weight loss was an accurate predictor of poor prognosis.⁴⁹

Regulate Blood Sugar to Slow Cancer Growth

There is a long-standing well-accepted link between elevated insulin levels and risk of cancer.⁵⁰

Cancer cells demonstrate a 3 to 5 fold increase in glucose uptake compared to healthy cells.⁵¹

Cancer thrives on glucose while also initiating gluconeogenesis and insulin resistance.⁵² Lipid based parenteral solutions for cancer patients slow cancer growth.

Modest ingestion of glucose (75 gm) caused a measurable decline in cell-mediated immunity in 7 healthy human volunteers. Mechanism of action is probably via elevated insulin, which competes with mitogens for binding sites on lymphocytes.⁵³

In animal studies, progressive increase in sucrose in the diet leads to a dose-dependent decline in antibody production.⁵⁴

Healthy human volunteers ingested 100 gram portions (average US daily intake) of simple carbohydrates from glucose, fructose, sucrose (white sugar), honey, and orange juice. While simple sugars signficantly impaired the capacity of neutrophils to engulf bacteria, starch ingestion did not have this effect.⁵⁵

In a study comparing 50 colorectal cancer patients to healthy matched controls, the cancer patients ate considerably more sugar and fat than the healthy people.⁵⁶

An epidemiological study of 21 countries suggests that high sugar intake is a major risk factor toward breast cancer.⁵⁷

Animals were fed isocaloric diets of carbohydrates. The group eating more sugar developed significantly more mammary tumors than the starch-fed group.⁵⁸

Risks of Nutrition Therapy

In an extensive review of the literature, Dr. Adrienne Bendich found the following data on nutrient toxicity⁵⁹:

• B-6 can be used at up to 500 mg (250 times RDA) for up to 6 years with safety.
• Niacin (as nicotinic acid) has been recommended by the National Institute of Health for lowering cholesterol at doses of 3000-6000 mg/day (150-300 times RDA). Time release niacin is more suspect of causing toxicity as liver damage.
• Vitamin C was tested in eight published studies using double blind placebo controlled design. At 10,000 mg/day for years, vitamin C produced no side effects.
• High doses of vitamin A (500,000 iu daily) can have acute reversible effects. Teratogenecity is the most likely complication of high dose vitamin A intake.
• Vitamin E intake at up to 3000 mg/day for prolonged periods has been shown safe.
• Beta-carotene has been administered for extended periods in humans at doses up to 180 mg (300,000 iu) with no side effects or elevated serum vitamin A levels.

In a separate review of the literature on nutrient toxicity by John Hathcock, PhD, a Food and Drug Administration toxicologist, the following data was reported⁶⁰:

• Vitamin A toxicity may start as low as 25,000 iu/day (5 times RDA) in people with impaired liver function via drugs, hepatitis, or protein malnutrition. Otherwise, toxicity for A begins at several hundred thousand iu/day.
• Beta-carotene given at 180 mg/day (300,000 iu or 60 times RDA) for extended periods produced no toxicity, but mild carotenemia (orange pigmentation of skin).
• Vitamin E at 300 iu/day (10 times RDA) can trigger nausea, fatigue, and headaches in sensitive individuals. Otherwise, few side effects are seen at up to 3,200 iu/day.
• B-6 may induce a reversible sensory neuropathy at doses of as low as 300 mg/day in some sensitive individuals. Toxic threshold usually begins at 2000 mg for most individuals.
• Vitamin C may induce mild and transient gastro-intestinal distress in some sensitive individuals at doses of 1000 mg (16 times RDA). Otherwise, toxicity is very rare at even high doses of vitamin C intake.
• Zinc supplements at 300 mg (20 times RDA) have been found to impair immune functions and serum lipid profile.
• Iron intake at 100 mg/day (6 times RDA) will cause iron storage disease in 80% of population. The "window of efficacy" on iron is probably more narrow than with other nutrients.
• Copper can be toxic, though dose is probably related to the ratio with other trace minerals.
• Selenium can be toxic at 1-5 mg/kg body weight intake. This would equate to 65 mg/day for the average adult, which is 812 times the RDA of 80 mcg. Some sensitive individuals may develop toxicity at 1000 mcg/day.
• Manganese can be toxic, though little specific information can be provided for humans.

Adjuvant Nutrition Improves the Effectiveness and/or Reduces the Toxicity from Medical Oncology

Vitamin C enhanced the chemotherapeutic action of levodopa methylester and increased survival time in B16 melanoma-bearing mice.⁶¹

Niacin supplementation in animals reduced the cardiotoxicity of the drug without inhibiting the effectiveness of the drug.⁶²

Low serum levels of vitamin A and E were indicative of human cancer patients who responded poorly to chemotherapy.⁶³

50 previously untreated cancer patients randomly received radiation therapy with or without 5 grams/day of vitamin C supplements. After 1 month, 87% of the vitamin C treated group showed a complete response (disappearance of all known disease) compared to 55% of the control.⁶⁴

Vitamin C and K separately showed anti-tumor activity against human cancer cells in vitro, but became synergistically effective at 2% the regular dosage when used together.⁶⁵

Vitamin C had no effect on the anti-tumor activity of adriamycin but did prolong the life of the animals treated with adriamycin.⁶⁶

B-6 deficient mice exhibited enhanced tumor susceptibility and increased tumor size.⁶⁷

22 patients with precancerous conditions, 19 patients with malignant oral lesions and 13 healthy controls were evaluated with respect to serum selenium levels and response to selenium therapy (300 mcg/day). Using selenium as sole therapy, there was a 38.8% objective response rate in treated patients.⁶⁸

Human prostatic cancer cells in vitro were markedly inhibited when vitamin E was added to the adriamycin.⁶⁹

Vitamin E enhanced the growth inhibitory effect of vincristine on mouse melanoma cells.⁷⁰

Vitamin E therapy (1600 iu/day) begun 5-7 days prior to therapy prevented 69% of adriamycin patients from experiencing baldness.⁷¹ Other studies have not always reached the same conclusion but have not followed this protocol. It appears important to begin vitamin E therapy at least 7 days prior to chemotherapy.

Calcium and vitamin D improved the efficacy of thioTEPA and other anti-neoplastic drugs against Hodgkin's disease and lung cancer.⁷²

Selenium supplements (200 mcg/day) in 23 patients with ovarian cancer or metastatic endometrial cancer showed less host tissue damage than the untreated group.⁷³

A derivative of ascorbic acid (sodium benzylideneascorbate, SBA) was given in daily dose of 200 mg/m2 to 55 patients with inoperable carcinoma. 8 patients achieved a complete response, 21 achieved partial response, 25 remained stable, and 1 showed progression of disease. The activity of this medication was increased with concurrent tamoxifen use.⁷⁴

While tamoxifen is the commonly used drug to inhibit estrogen-dependent tumor growth, vitamin C has clearly demonstrated the ability to inhibit estrogen-dependent tumor growth in hamsters.⁷⁵

Vitamin E and selenium helped reduce the lipid peroxidation-induced cardiotoxicity from adriamycin in animal models without inhibiting effectiveness of therapy.⁷⁶

Potassium bromate can cause nephrotoxicity via renal oxidative DNA damage. In rat model, pre and post treatment with cysteine and glutathione (amino acids) and vitamin C protected against oxidative damage in the kidneys.⁷⁷

Niacin (vitamin B-3) as nicotinamide is able to dramatically improve the response of hypoxic radioresistant tumors in animal models. Anaerobic tumors do not respond well to radiation therapy, while niacin seems to improve aerobic metabolism to make solid tumors more vulnerable to radiation therapy.⁷⁸

Vitamin E topically applied (400 mg per lesion, twice daily for 5 days) to oral lesions induced by chemotherapy provided substantial relief in 6 of 9 patients while only 1 of 9 placebo treated patients had any relief from oral mucositis. Vitamin E seemed to best help patients taking cisplatin and 5-fluorouracil. Oral mucositis is often the beginning of anorexia which deteriorates into clinical malnutrition.⁷⁹

In mouse and guinea pig models, vitamin C prolonged the life of animals treated with adriamycin without affecting the anti-tumor activity of this drug. Vitamin C was able to prevent the adriamycin-induced cardiomyopathy as determined by electron microscopy.⁸⁰

While tamoxifen is a drug that binds up circulating estrogen, which can incite tumor growth, studies show that wheat fiber does the same thing while also reducing secondary bile acids and bacterial enzymes associated withcolon cancer--without the potential carcinogenic effects of tamoxifen.⁸¹

Nutrients have a Profound Impact on the Immune System

Alexander, JW, et.al., Nutritional immodulation in burn patients, Critical Care Medicine, voll.18, no.2, pg.149, 1990

Alexander, JW, Nutrition and Infection, Archives of Surgery, vol.121, p.966, Aug.1986

Alexander, JW., Nutrition and infection: new perspectives for an old problem, Archives of Surgery, vol.121, pg.966, 1986

Baehner, RL, Autooxidation as a basis for altered function by polymorphonuclear Leukocytes, Blood, vol.50, no.2, p.327, Aug.1977

Barone J, et.al., Dietary fat and natural-killer-cell activity, Americian Journal Clinical Nutrition, vol.50, no.4, pg.861, Oct.1989

Beisel WR, Single nutrients and immunity, American Journal Clinical Nutrition, vol.35, (Suppl.), pg.417, 1982

Beisel, WR, et al., Single-Nutrient effects on immunologic functions, Journal of the American Medical Association, vol.245, no. 1, p.53, Jan.2, 1981

Beisel, WR, Single nutrients and immunity, American Journal Clinical Nutrition, vol.35, p.417, Feb. supp, 1982

Beisel, WR, The history of nutritional immunology, Journal of Nutritional Immunology, vol.1(1), p.5, 1992

Bendich, A., Anti-oxidant vitamins and immune responses, in NUTRITION AND IMMUNOLOGY, p.125, Liss, NY, 1988

Bower, RH, Nutrition and immune function, Nutrition in Clinical Practice, vol.5, no.5, pg.189, 1990

Bowman, TA, et.al., Vitamin A deficiency decreases natural killer cell activity and interfon production in rats, Journal Nutrition, vol.120, no.10, p.1264, Oct. 1990

Carver, JD, et.al., Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation, Journal of Parenteral and Enteral Nutrition, vol.14, no.1, pg.18, Jan.1990

Cerra, FB, et.al., Effect of enteral nutrient on in vitro tests of immune function in ICU patients: a preliminary report, Nutrition, vol.6, no.1, pg.84, 1990

Cerra, FB, Immune system modulation: nutritional and pharmacologic approaches, Critical Care Medicine, vol.18, no.2, Jan.1990

Cerra, FB, Nutrient modulation of inflammatory and immune function, Americian Journal of Surgery, vol.161, p.230, Feb.1991

Chandra RK, ed., Comtemporary issues in clinical nutrition, vol.11, NUTRITIONAL IMMUNOLOGY, New York, Alan R. Liss, Inc., 1988

Chandra RK, Nutrition, immunity and outcome; past, present and future, Nutrition Research, vol.8, no.3, pg.225, 1988

Chandra, RK, et.al., Effect of two feeding formulas on immune responses and mortality in mice challenged with listeria monoclytogenes, Immunology Letters, vol.27, pg.45, 1991

Chandra, RK, Immunodeficiency in Undernutrition and Overnutrition, Nutrition Reviews, vol.39, no.6, pg.225, June 1981

Chandra, RK, Nutrition and immunity-basic considerations. Part 1., Contemporary Nutrition, vol.11, no.11, 1986

Chang, KJ, et.al., Comparison of the effect of lipoxygenase metabolites of arachidonic acid and eicosapentaenoic acid on human natural killer cell cytotoxicity, Prostaglandins Leukotrienes Essentially Fatty Acids, vol.38, no.2, pg.87, Nov.1989

Chang, KJ, et.al., Role of 5-lipoxygenase products of arachidonic acid in cell-to-cell interaction between macrophages and natural killer cells in rat spleen, Journal Leucocyte Biology, vol.50, no.3, pg.273, Sept.1991

Chang, KJ, et.al., Effect of oral ingestion of eicosapentaenoic acid-ethyl ester on natural killer cell activity in rat spleen cells, Prostaglandins Leukotrienes Essential Fatty Acids, vol.37, no.1, pg.31, July 1989

Chowdhury, BA, et.al., Effect of zinc administration on cadmium-induced suppression of natural killer cell activity in mice, Immunology Letters, vol.22, no.4, pg.287, Oct.1989

Christou, N, Perioperative nutritional support: immunologic defects, Journal of Parenteral and Enteral Nutrition, vol.14, no.5, supp., Sept.1990

Cifone, MG., et.al., In vivo cadmium treatment alters natural killer activity and large granular lymphocyte number in the rat, Immunopharmacology, vol.18,no.3, pg.149, Nov-Dec.1989

Daly, JM, etl.al., Enteral nutrition with supplemental arginine, RNA and Omega-3 fatty acids: a prospective clinical trial, Journal of Parenteral and Enteral Nutrition, vol.15, no.1, pg. 19S, 1991

Garre MA, et.al., Current concepts in immune derangement due to undernutrition, Journal of Parenteral and Enteral Nutrition, vol.11, no.3, pg.309, 1987

Gershwin ME, et.al., NUTRITION AND IMMUNITY, Orlando, Academic Press, Inc., 1985

Ghoneum, M., et.al., Suppression of murine natural killer cell activity by tributyltin: in vivo and in vitro assessment, Environmental Research, vol.52, no.2, p.178, Aug.1990

Gottschlich MM, Differential effects of three enteral dietary regimens on selected outcome variables in burn patients, Journal of Parenteral and Enteral Nutrition, vol.14, no.3, pg.225, 1990

Hallquist, NA, et.al., Maternal-iron-deficiency effects on peritoneal macrophage and peritoneal natural-killer-cell cytotoxicity in rat pups, Americian Journal Clinical Nutrition, vol.55, no.3, pg.741, March, 1992

Halstead, BW, immune augmentation therapy, Journal International Academy Preventive Medicine, vol.9, no.1, pg.5, 1985

Ilback, NG, Effects of methyl mercury exposure on spleen and blood natural killer (NK) cell activity in the mouse., Toxicocology, vol.25, no.1, pg.117, March 1991

Immune system modulation: symposium on nutritional and pharmacologic approaches, Critical Care Medicine, vol.18, no.2, (S) pg.85, 1990

Kafkewitz, D., et.al., Deficiency is immunosuppressive, American Journal Clinical Nutrition, vol.37, pg.1025, 1983

Katz, DP, et.al., Enteral nutrition: potential role in regulating immune function, Current Opinion in Gastroenterology, vol.6, pg.199, 1990

Kelly, C. et al, Immunosuppression in the surgical oncology patient, Nutrition and Immunology Digest, vol.1, no.2, 1991

Kennes, B, et.al., Effect of vitamin C supplements on cell-mediated immunity in old people, Gerontology, vol.29, no.5, pg.305, 1983

Kinney, JM, et.al., NUTRITION AND METABOLISM IN PATIENT CARE,Philadelphia, W.B. Saunders Co., 1988

Kulkarni, AD, et.al., Influence of dietary glutamine and IMPACT, on in vivo cell-mediated immune response in mice, Nutrition, vol.6, no.1, pg.66, 1990

Levy, JA., Nutrition and the immune system, in Stites DP et al., Basic and Clinical Immunology, 4th Edition, Los Altos, Ca., Lange Medical Publications, pg.297, 1982

Lieberman, MD, Effects of nutrient substrates on immune function, Nutrition, vol.6, no.1, pg.88, 1990

Meadows GG, et.al., Ethanol induces marked changes in lymphocyte populations and natural killer cell activity in mice, Alcohol Clinical Exp Research, vol.16, vol.3, p.47, June 1992

Muzzioli, M., et.al., In vitro restoration by thymulin of NK activity of cells from old mice, International Journal of Immunopharmacol, vol.14, no.1, pg.57, Jan.1992

Nair, MP, et.al., Immunoregulation of natural and lymphokine-activated killer cells by selenium, Immunopharmacology, vol.19, no.3, pg.177, May-June, 1990

Nutrition and the immune response, Dairy Council Digest, vol.56, no.2, March-April, 1985

Nuwayri-Salti, N., et.al., Immunologic and anti-immunosuppressive effects of vitamin A, Pharmacology, vol.30, no.4, pg.181, 1985

Palombo, JD, et.al., (Collective Review), Endothelial cell factors and response to injury, Surgery, Gynecology & Obstetrics, Vol.173, p.505, Dec. 1991

Petrie, HT, et.al., Selenium and the immune response: 2. Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo, Journal Leucocyte Biology, vol.45, no.3, pg.215, March 1989

Petrie, HT, Selenium and the immune response: Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo, Journal Leucocyte Biology, vol.45, no.3, p.215, March, 1989

Randall, HT, Enteral nutrition: tube feeding in acute and chronic illness, Journal of Parenteral and Enteral Nutrition, vol.8, no.2, pg.113, 1984

Reynolds, JV, The influence of protein malnutrition on T cell, natural killer cell, and lymphokine-activated killer cell function, and on biological responsiveness to high-dose interleukin-2, Cellular Immunology, vol.128, no.2, pg.569, July 1990

Riley, ML, et.al., Failure of dietary restriction to influence natural killer activity in old rats, Mechanisms of Ageing and Development, vol.50, no.1, pg.81, Oct.1989

Roth, JA, et.al., In vivo effect of ascorbic acid on neutrophil function in healthy and dexamethasone-treated cattle, American Journal Veterinary Research, vol.46, no.12, Dec., 1985

Schlichter, LC, et.al., Interactive effects of Na and K in killing by human natural killer cells, Experimental Cell Research, vol.184, no.1, pg.99, Sep.1989

Schriever, MM, et.al., Natural killer cells, vitamins, and other blood components of vegetarian and omnivorous men, Nutrition Cancer, vol.12, no.3, p.271, 1989

Spear, AT, et.al., Iron deficiency alters DMBA-induced tumor burden and natural killer cell cytotoxicity in rats, Journal Nutrition, vol.122, no.1, pg.46, Jan.1992

Talbott, MC, et.al., Pyridoxine supplementation: effect on lymphocyte responses in elderly persons, Journal of Clinical Nutrition, vol.46, p. 659, 1987

Update on Immunonutrition symposium, Nutrition, vol.6, no.1, pg.1, 1990

Vijayaratnam, V., et.al., The effects of malnutrition on lymphoid tissues, Nutrition, vol.3, no.3, pg.213, 1987

Wagner, PA, et.al., Zinc nutriture and cell-mediated immunity in the aged, International Journal Vitamin Nutrition Research, vol.53, no.1, pg.94, 1983

Wan, JMF, et.al. Symposium on the interaction between nutrition and inflammation, Proceedings of the Nutrition Society, vol.48, p.315, 1989

Watson, RR, Immunological enhancement by fat-soluble vitamins, minerals, and trace metals,Cancer Detection and Prevention, vol.9, p.67, 1986

Wollschlager, C, et.al., A lipid, arginine and RNA supplemented enteral formula (IMPACT) alters airway colonization in intubated patients, Americian Review of Respiratory Diseases, 141:334A, 1990

Yamashita, N. et.al., Effect of eicosapentaenoic and docosahexaenoic acid on natural killer cell activity in human peripheral blood lymphocytes, Clinical Immunology Immunopathology, vol.59, lno.3, pg.335, June 1991

Yirmiya, R., et.al., Ethanol increases tumor progression in rats: possible involvement of natural killer cells, Brain Behavior Immun, vol.6, no.1, pg.74, March 1992

Many nutrients taken orally can provide pharmacological changes in immune function in humans. Protein, arginine, glutamine, omega-6 and omega-3 fats, iron, zinc, vitamins E, C, and A have all been proven to modulate immune functions.⁸²

Vitamin A deficiency causes reduced lymphocyte response to antigens and mitogens, while beta-carotene supplements stimulate immune responses.⁸³

There is extensive literature supporting the importance of vitamin B-6 on the immune system. In one study, B-6 supplements (50 mg/day) provided a measurable improvement in immune functions (T3 and T4 lymphocytes) for 11 healthy well fed older adults.⁸⁴

Various B vitamins have been linked to the proper functioning of antibody response and cellular immunity.

Folate deficiency decreases mitogenesis.

Deficiency of vitamin C impairs phagocyte functions and cellular immunity.

Vitamin E deficiency decreases antibody response to T-dependent antigens, all of which gets worse with the addition of a selenium deficiency. In test animals, normal vitamin E intake was not adequate to optimize immune functions.⁸⁵ Modest supplements of vitamin E have been shown to enhance the immune response.

While iron deficiency can blunt immune functions, iron excess can increase the risk for cancer.⁸⁶

Zinc exerts a major influence on the immune system. Lymphocyte function is seriously depressed and lymphoid tissues undergo general atrophy in zinc-deficient individuals. The lymphocytes in zinc-deficient animals quickly lose their killing abilities (cytotoxicity) and engulfing talents (phagocytosis) for tumor cells and bacteria. Natural killer cell and neutrophil activity is also reduced. All of these compromised immune activities elevate the risk for cancer.

Copper plays a key role in the production of superoxide dismutase and cytochrome systems in the mitochondria. Hence, a deficiency of copper is manifested in a depressed immune system, specifically reduced microbicidal activity of granulocytes.

Selenium works in conjunction with vitamin E to shield host cells from lipid peroxidation. Humoral immune response is depressed in selenium deficient animals. Selenium and vitamin E deficiencies lead to increased incidence of enteric lesions. Lymphocyte proliferation is reduced in selenium deficiency. The theory is that selenium and vitamin E help to provide the host immune cells with some type of "bullet proof plating" against the toxins used on foreign cells. Hence, one immune body can live on to destroy many invaders if enough vitamin E and selenium allow for these critical chemical shields.

In magnesium deficiency, all immunoglobulins (except IgE) are reduced, along with the number of antibody forming cells. Magnesium is crucial for lymphocyte growth (involvement in protein metabolism) and transformation in response to mitogens. Prolonged magnesium deficiency in animals leads to the development of lymphomas and leukemia.

Iodine plays an important role in the microbicidal activity of polymorphonuclear leukocytes. Activated neutrophils may use the conversion of iodide to iodine to generate free radicals for killing foreign invaders.

Boron is an interesting trace mineral, since it is now recognized for its role in preventing osteoporosis, yet is still not considered an essential mineral. Boron deficiency in chicks creates immune abnormalities like arthritis.

Toxic trace minerals, like cadmium, arsenic and lead all blunt the immune system.

The quality and quantity of fat in the diet plays a major role in dictating the health of the immune system. A deficiency of the essential fatty acid (linoleic acid) will lead to atrophy of lymphoid tissue and a depressed antibody response. And yet excess intake of polyunsaturated fatty acids will also diminish T-cell immune responsiveness. Since fat directly affects prostaglandin pathways, and prostaglandins (depending on the pathway) can either depress or enhance immune function, fat intake is crucial in encouraging a healthy immune system. Oxidized cholesterol is highly immuno-suppressive. Cholesterol is less likely to oxidize while in the presence of anti-oxidants, like vitamin E, C, and beta-carotene.

Basically, nutrition plays a key role in the effectiveness of the immune system. Primary assessment techniques to find the relative nutrient status of the immune system include:

• Clinical: dietary intake, physical examination
• Anthropometric: skin fold thickness, percent body fat
• Hematologic: hemoglobin and ferritin levels
• Biochemical: serum albumin, serum transferrin, creatinine/height index, zinc status
• Immunologic: lymphocyte count, terminal transferase activity, T-cells
• Miscellaneous: hand grip strength, dark adaptation, taste acuity

A main goal of this nutrition program is to optimize the functioning of the immune system via foods and nutritional supplementation (pills, powder, or TPN). A healthy immune system is better able to join in the battle to rid the body of tumor cells.

Therapeutic Supplements may help Cance Patients

VITAMINS
Vitamin E.

Was used (via injections) to reverse oral tumor progress in animals with induced tumors.⁸⁹

Prevents and may even reverse tumor growth in animals with chemically induced tumors.⁹⁰

Was able to prevent expected tumors in lab animals exposed to DMBA.⁹¹

Increased the effectiveness and specific toxicity of chemotherapy agents on tumors in culture.⁹²

Relieves most cystic breast disease, which indicates that E can treat pre-cancerous conditions.⁹³

May be anti-neoplastic by virtue of its ability to protect the prostaglandin prostacyclin.⁹⁴

Protects against damage from radiation therapy.⁹⁵

In combination with selenium was able to prevent expected tumors in animals after DMBA injections.

Significantly elevated the microsomal hydroperoxidase activity.⁹⁶

And selenium provided partial protection against cardiotoxicity in adriamycin use on rabbits. Best protection was aforded by high dose vitamin E.⁹⁷

Deficiency accentuated the cardiotoxicity of adriamycin in rats.⁹⁸

Increased (in vitro) the therapeutic benefits of chemotherapy agents on human prostate cancer cells.⁹⁹

Directly stunted the growth of mouse melanoma cells in vitro.¹⁰⁰

Topical application of DMSO and vitamin E produced a 68% decrease in skin necrosis on mice given adriamycin.¹⁰¹

Mice with oral cancer were supplemented with injections of vitamin E, beta-carotene, canthaxanthin, and algae extract. Major improvements in tumor necrosis factor were measured in the supplemented mice, who also experienced varying levels of tumor regression.¹⁰²

Reduced the cardiotoxic effects of daunomycin (similar to adriamycin) in test animals.¹⁰³

And vitamin K3 (menadione) enhanced the anti-metabolic activity of the chemotherapy agents 5FU and leucovorin in vitro.¹⁰⁴

Sensitized tumor cells, but not healthy cells, to radiation therapy for enhanced effectiveness.¹⁰⁵

Use in radiation therapy reduces toxic side effects.¹⁰⁶

Patients with peripheral neuropathy (common as a side effect for certain chemo agents) were found to be clinically low in vitamin E in the region of nerve damage.¹⁰⁷ Nerve numbness in cancer patients may be due to the elevated need for vitamin E during chemotherapy.

Elevates lymphocyte proliferation in animals.¹⁰⁸

Vitamin E, A, and prenylamine blunted the cardiotoxic effects of adriamycin in rabbits.¹⁰⁹

Provided measurable protection against the cardiotoxicity of adriamycin in rabbits.¹¹⁰

Using 1600 iu/day of vitamin E, hair loss in cancer patients was reduced from the typical 90% to 30% in the treated group.¹¹¹

Toxicity. Human studies show no side effects from vitamin E at levels up to 3200 mg/day (3200 iu/day).¹¹²

Vitamin K

The primary function of K is as a coagulating factor in the prothrombin cascade in the blood. A normal diet combined with bacterial fermentation in the distal small bowel appears to provide "adequate" levels of K to prevent hemorrhage.¹¹³

Normal daily intake is difficult to estimate since an undetermined amount of K is produced through bacterial fermentation. However, the National Academy of Sciences estimates that the average American diet contains 300-500 mcg/day. ¹¹⁴

Vitamin K exists in 3 distinct chemical analog forms with the following differences

K-1 (phylloquine or phytonadione, relatively non-toxic, preferred form for non-pharmacological purposes)

K-2 (menaquinone, produced by bacterial fermentation in the gut, does not inhibit DNA synthesis in malignant cells)

K-3 (menadione, synthetic derivation, accumulates in the liver, can be toxic, is most effective as an anti-neoplastic agent).

Additionally, over the past thirty years, evidence has been gathering that K has anti-neoplastic properties. ¹¹⁵

Common deficiencies.

K deficiency is common in patients with general malnutrition, intestinal malabsorption, or treatment with anti-biotics.¹¹⁶

A profound deficiency of vitamin K was found in 34 cancer patients on anti-microbial therapy.¹¹⁷

Therapeutic doses of vitamin E elevate the need for vitamin K.¹¹⁸

Therapeutic levels required to reverse hemorrhagic clinical vitamin K deficiency range from 20-50 mg/day of K.

Use in cancer treatment.

When vitamin K (as Synkavite, menadione, K-3) was given to human cancer patients IV at a 50-100 mg dosage prior to radiation therapy, 5 year survival increased from 20% of the patients without K to 39% of the matched group given radiation plus vitamin K. ¹¹⁹

Counterindications.

Vitamin K-1 (not K-3) supplements will reduce the effectiveness of anti-coagulants at lengthening prothrombin clotting time. Vitamin K-1 (phytonadione) at 1 mg/day does not present any hazard to patients receiving anti-coagulant therapy.¹²⁰ According to Dr. Chlebowski, vitamin K enhances the anti-metastatic effects of anti-coagulants.

Vitamin C.

In animals with implanted Ehrlich carcinoma and L1210 leukemia, injections of vitamin B-12 (hydroxocobalamin) and vitamin C (dehydroascorbic acid) provided dramatic improvements in survival of the animals. By day 19, all 20 of the control animals were dead, while 50% of the treated mice survived 60 days or more. This nutrient combination has a precedence for limiting tumor growth without affecting the host.¹²¹

Potentiates the value while reducing the toxicity of chemotherapy in animal studies.¹²²

Potentiates the value of radiation therapy.¹²³

Using chemotherapy in conjunction with nutritional therapy, supplemental levels of vitamins A (Aquasol A 400,000 iu/day), C (8 gm/day), and E (3200 iu/day) were provided to 20 cancer patients over the course of 12 months with 7 (35%) experiencing complete remission, 8 (40%) partial remission, and 5 (25%) failed. Only one patient experienced any symptoms attributed to the mega-vitamin therapy.¹²⁴

Mice with induced liver cancer were then pre-treated with vitamins C and K3 (menadione) before using various chemotherapy drugs. The nutrients provided considerable protection while enhancing the effectiveness of the treatment.¹²⁵ Postulated mechanisms include the attack on catalase-deficient cancer cells by the combination of vitamin C and K3.

Vitamin C, thiamin, and cysteine provided nearly complete protection against free radical acetylaldehyde destruction in animals.¹²⁶

Vitamin C (10 gram/day) provided life extension and improvement of quality of life in 100 terminal cancer patients.¹²⁷ Other studies have not had such promising results. Possible explanations for the discrepancy may be that the other studies used patients who had been heavily pre-treated with chemo and radiation therapy and considered unresponsive and terminal.

Vitamin C and E provide measurable protection against the carcinogen PCB in various animals.¹²⁸

2-3 grams daily of ascorbate provided stimulation of lymphocyte transformation to certain mitogens.¹²⁹

After 9-12 months on 3 grams daily of vitamin C supplements, rectal polyps were reduced in the treated group by 74% compared to the untreated group reduction of 31%.¹³⁰

Ascorbic acid supplements in cancer patients provided improvements in minor symptoms, pain control, and quality of life.¹³¹

Vitamin C supplements provided protection against the cytotoxic effects of methotrexate in mice.¹³²

Toxicity. Most patients can tolerate 10-20 grams orally. Other patients will experience mild intestinal distress at these levels. Up to 100 grams has been used in TPN formulas.

Bioflavonoids

Quercetin increased the cell kill rate in cancer cells (in vitro) exposed to hyperthermia (heat therapy) with no effect on normal healthy cells.¹³³

Quercetin inhibited cancer in animals exposed to two carcinogens.¹³⁴

Quercetin caused inhibition of growth (in vivo) in two squamous cell carcinoma lines.¹³⁵

Several bioflavonoids (including quercetin) were able to inhibit DNA binding from benzopyrenes. ¹³⁶

Vitamin A

Of 102 people who had bladder cancer, the incidence of recurring tumors was 1.8 times higher in those who consumed the lower amounts of vitamin A.¹³⁷

Nine male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13 cis-retinoic acid (analog of vitamin A) without other medical intervention. 60 weeks later, immune function had improved and progress against the tumor had been made.¹³⁸

Vitamin A in combination with BCG suppressed tumor growth in the lung tumors of animals. Vitamin A alone did not affect tumor growth, but only in conjunction with BCG.¹³⁹

Vitamin A prevented impaired wound healing in post-operative and irradiated rats. Vitamin A provided continuous high level of immune competence throughout the normal immunosuppressive phase.¹⁴⁰

Vitamin A supplements provided complete or partial remission in patients with benign breast disease.¹⁴¹

Toxicity. 300,000 iu/day of retinol palmitate (preformed vitamin A) administered to 138 lung cancer patients for at least 12 months produced occasional dry skin, but no significant side effects.¹⁴² Toxicity may begin at levels of 500,000 iu/day (100 times the RDA) long term intake for adults, and proportionately less in children.¹⁴³ Toxicity usually involves consumption of 200,000 iu/day for many days, though individuals with compromised immune function may develop toxicity at 25,000 iu.¹⁴⁴ Toxicity of A can be reduced by higher intake of vitamin E to mitigate lipid peroxide effects.

Beta carotene

2500 iu of beta-carotene = 250 retinol equivalents =1.5 mg. Beta-carotene has been shown to protect phagocytic cells from auto-oxidative damage, enhance T and B lymphocyte proliferation, enhance macrophages, interleukin production, and natural killer cell tumoricidal abilities.¹⁴⁵

Beta-carotene probably has effectiveness against cancer as a chain-breaking anti-oxidant.¹⁴⁶

Vitamin A intake protected workers who were smokers and/or exposed to toxic chemicals against lung cancer. Beta-carotene provided a more protective edge than animal sources of vitamin A.¹⁴⁷

Using combined supplements of beta-carotene and canthaxanthin, Italian researchers found that cancer patients who had undergone surgery with radiation therapy had a much higher than anticipated survival rate and level of health.

A review of the literature on vitamin A and beta-carotene shows that beta-carotene has anti-oxidant and immune stimulating properties that are not found in vitamin A. Perhaps these are two distinct nutrients.¹⁴⁸

Beta-carotene has been shown to protect animals against ultra-violet induced skin tumors and carcinogen treatment by preventing malignant transformation and nuclear damage.¹⁴⁹

Beta-carotene and algae extracts injected into DMBA-provoked tumors in hamsters caused regression of the tumors.¹⁵⁰

Toxicity. Toxicity of beta-carotene has never been found, since it is not mutagenic, carcinogenic, embryotoxic, or teratogenic and does not cause hypervitaminosis A.¹⁵¹

15 mg daily of oral supplements of beta-carotene (25,000 iu.) provided a 10 fold increase in serum beta-carotene without any skin discoloration.¹⁵²

People have consumed 300,000 iu (180 mg) of beta-carotene daily for 15 years with no adverse side effects. In the few beta-carotene reactions, it is always with excess consumption of food components (like carrot juice), which makes other food components and not the beta-carotene suspect in these mild toxicity reactions. Pure beta-carotene supplements have never produced toxicity in any human studies.

B-6 (pyridoxine)

While earlier findings indicated that a B-6 deficiency would slow down tumor growth¹⁵³ and increase survival in animals with cancer¹⁵⁴, more recent findings indicate the opposite. Animals fortified with B-6 and then injected with melanoma cells showed a greater resistance to this deadly form of cancer.¹⁵⁵

B-6 inhibited melanoma cells in vivo.¹⁵⁶

Vitamin B-6 displays important immune modulating activity of the immune system.¹⁵⁷

Vitamin B-6 at 25 mg/day for 33 bladder cancer patients provided marked improvement in cancer recurrence over the control group.¹⁵⁸

Vitamin B-6 kills hepatoma cells (in vitro).¹⁵⁹

Administered as an ointment on a human melanoma patient four times daily for a two week period resulted in disappearance of the cutaneous papules.¹⁶⁰

High dose supplements (300 mg/day) provided considerable relief from the toxicity of radiation therapy.¹⁶¹

Pyridoxine deficiency produces increased tumor resistance.¹⁶²

Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B-6 status.¹⁶³

B-6 inhibits the growth of human malignant melanoma cell line.¹⁶⁴

B-6 significantly inhibited melanoma cells lines (in vitro) and may be an effective anti-neoplastic agent.¹⁶⁵

B-6 (300 mg/day) administered throughout the 8 week radiation therapy course for human endometrial cancer patients improved survival by 15% at 5 years.¹⁶⁶

Toxicity. Less than 500 mg/day in humans appears to be safe.¹⁶⁷ 300 mg/day provide maximal protection against radiation therapy.

MINERALS

Selenium.

High dose supplementation (equivalent to 54 mg/day in humans) resulted in 83-90% reduction in the rate of tumor growth in mice.¹⁶⁸

In mice fed either a high or low PUFA fat diet, selenium provoked a drop in tumor incidence in both groups. Selenium apparently exerts a cancer-protective role beyond its antioxidant function in lipid metabolism.¹⁶⁹

Enhanced drug detoxification pathways (conjugative, not by P450) in animals.¹⁷⁰

Reduces the toxicity of paraquat (an herbicide).¹⁷¹

In animal studies could (a) inhibit both the initiation and promotion phases of cancer, (b) continuous intake of selenium was necessary to achieve maximum protection, (c) inhibit the re-appearance of tumors after surgery.¹⁷²

Provided fewer DNA strand breaks and greater repair of broken DNA than unsupplemented or less supplemented hamsters.¹⁷³

Administration of sodium selenite (equivalent to 120 mg for an adult) inhibited the growth of leukemia cells and increased the longevity of test mice.¹⁷⁴

Mega-doses effectively limited tumor growth in mice with Ehrlich ascites tumors. Although high dose selenium supplementation did not affect the growth of healthy normal animals, it did have a definite retarding effect on rapidly dividing cells.¹⁷⁵ Selenium may be an important anti-proliferative factor to squelch rapidly dividing tumor cells.

Provided considerable protection against the toxic effects of cis-platinum, allowing the lethal dose to kill half the animals (LD50) to increase from 9.3 to 17.5 mg/kg, thus allowing higher and more effective doses of chemotherapeutic agents.¹⁷⁶

In mice provided measurable improvements in natural killer cytotoxicity in spleen cells (70% improvement over unsupplemented mice), specific T-lymphocyte cytotoxicity, and other immune parameters that could be therapeutic against cancer.¹⁷⁷

Toxicity. The National Academy of Sciences indicates that long-term daily intake of 5000 micrograms of selenium may result in fingernail changes and hair loss. Extrapolated from animal studies, 7 mg (7000 mcg) in humans may halt tumor progression. Selenite is more toxic than selenium bound to amino acids (i.e. selenomethionine). Ingestion of 1-5 mg/kg body weight of selenite will likely produce toxic side effects (65,000 mcg in the 65 kg adult).

FATTY ACIDS

EPA (eicosapentaenoic acid).

A diet high in menhaden oil (20% of kcal) promoted major increases in cytochrome P450 in test animals.¹⁷⁸

For one week pre-operative and 4 weeks after tumor implantation, varying levels of EPA and DHA from fish oil induced significant reduction in the weight and volume of the implanted mammary tumors in test animals.¹⁷⁹

EPA slowed tumor growth in mice with inoculated human colon cancer.¹⁸⁰

EPA slowed tumor growth and prolonged survival in mice with transplanted human metastatic breast cancer.¹⁸¹

EPA in conjunction with anti-human milk fat globule monoclonal antibodies offered the greatest reduction in tumor size (36% below corn oil or lard diets) in mice innoculated with human breast tumors.¹⁸²

EPA diet significantly lowered the level of estradiol (a putative breast tumor marker) in 25 women at risk for breast cancer.¹⁸³

EPA has protective effects against the development and/or progression of various animal tumor models studied.¹⁸⁴

EPA produced a significant decrease in the development of both the size and number of preneoplastic lesions in animals in induced tumors.¹⁸⁵

EPA reduced the size and number of tumors while increasing the tumor latent period in rats fed various types of fat in the diet, then exposed to carcinogens.¹⁸⁶

EPA-fed rats had significant reduction in the growth of induced tumors.¹⁸⁷

EPA-fed mice had significant slowing of tumor growth.¹⁸⁸

EPA slowed tumor growth in transplanted mammary tumors in rats.¹⁸⁹

EPA inhibited the development of tumors in athymic mice inoculated with human breast cancer. EPA also had a synergistic effect with Iodine 131 labeled monoclonal antibodies in reducing tumorogenesis.¹⁹⁰

EPA rich diet significantly depressed growth rate of human breast tumors transplanted into animals. Tumors in EPA-fed animals are more responsive to chemotherapy agents (mitomycin C, doxorubicin).¹⁹¹

EPA reduced tumor growth in transplanted human colon cancer into mice.¹⁹²

EPA-fed animals had fewer and smaller lesions after induced cancer.¹⁹³

EPA slowed tumor growth in animals even when administered several months after tumor induction.¹⁹⁴

EPA reduced the weight and volume of tumors in transplanted human prostatic cancer to animals.¹⁹⁵

EPA retarded the development of human prostatic cancer that was inoculated in animals.¹⁹⁶

EPA reduced both the frequency and rate of metastasis of transplanted tumors in animals.¹⁹⁷

EPA improves the response of tumor cells to hyperthermia and chemotherapeutic agents by altering the properties of the tumor cell membrane.¹⁹⁸

EPA increases the adriamycin kill rate on cultured human leukemia cells.¹⁹⁹

EPA substantially reduced the invasiveness of cultured human tumor cells (both malignant murine melanoma and fibrosarcoma).²⁰⁰

EPA and GLA separately were able to selectively kill cultured human tumor cells.²⁰¹

EPA and GLA enhanced the tumoricidal effects of anticancer agents in vitro.²⁰²

EPA and GLA were selectively toxic to human breast, lung, and prostate cancer cells in vitro. The fatty acids also enhanced the cytotoxic activity of cytotoxic drugs on tumor cells.²⁰³

EPA and GLA suppressed the growth of cultured human larynx cancer cells.²⁰⁴

DHA (accompanying fatty acid with EPA in fish oil) was able to partially reverse adriamycin-resistant small cell lung carcinoma cells in vitro.²⁰⁵

EPA modulates estrogen metabolism for reduced risk in breast cancer.²⁰⁶

EPA rich diet can slow tumor growth through modulation of both tumor protein synthesis and breakdown.²⁰⁷

EPA may have a beneficial role as adjunctive anti-neoplastic therapy in breast cancer.²⁰⁸

EPA provided higher survival (7 of 11 versus 2 of 11 in control group) of guinea pigs injected with endotoxin²⁰⁹.

EPA provided higher survival (87% versus 63% in control group) for guinea pigs injected with endotoxin.²¹⁰

EPA provided higher survival (83% versus 50% in control group) for guinea pigs injected with endotoxin.²¹¹

How Does the EPA Slow Tumor Growth?
Proposed Mechanisms

Altering membrane fluidity in healthy and/or tumor cells to change the basic cellular metabolism.

By altering membrane fluidity, can change the response of tumor cells to growth factors, hormones, antibodies.

Alters prostaglandin output, with more anti-inflammatory and anti-aggregatory eicosanoids.

Perhaps by prostaglandin metabolism, reduces the "stickiness" (aggregation) of cancer cells, to retard their metastatic abilities. Amount of EPA necessary for the average adult to have measurable reduction in cell aggregation (stickiness): 2-4 gm/day. Gorlin, R., Archives of Internal Medicine, vol.148, p.2043, Sept.1988

Stimulates the immume system.

Alters bile acid metabolism (may be important in colon cancer).

May be directly toxic to tumor cells, which have altered capacity to use any type of fats. Without proper use of fat soluble antioxidants, tumor cells may find the highly unsaturated fatty acids of EPA to be like an internal "hand grenade".

Attenuates shock from lactic acidosis in endotoxin-exposed animals. May buffer the impact of cytotoxic drugs on human cancer patients.

Alters hormonal balance for estrogen and testosterone dependent tumors.

Counterindications for the use of EPA

Can induce vitamin E deficiency, unless supplements of E are added. Suggested dosage: 400 iu vitamin E per every 2500 mg EPA.

Reduces platelet aggregation and slows normal blood clotting. High dose counterindicated for patients anticipating surgery.

Yetiv, JZ, Journal of the American Medical Association, vol.260, p.665, Aug.5, 1988

Toxicity A one gram capsule of fish oil usually provides 240-600 mg of EPA. Intake of 6000 mg of EPA may inhibit blood clotting, hence may be counterindicated in patients due for surgery. A minimum of 1000 mg daily of EPA must be consumed to expect any beneficial effects. EPA to GLA in a ratio of 5:1 may encourage the production of prostaglandin PGE-1 for immune stimulating effects.

GLA (gamma linolenic acid)

Combined intake with vitamin C was able to double the mean survival time for patients with primary hepatic carcinoma.²¹²

Provided subjective and objective improvements in 21 patients with untreatable malignancies.²¹³

GLA plus iron supplements dramatically increased the tumor cell kill rate with in vitro studies on human cancers, opening the possibility to a relatively safe and selectively toxic cancer regimen.²¹⁴

Varying combinations of GLA and EPA were able to provide a high cancer cell kill rate in vitro.²¹⁵

Toxicity. A one gram capsule of evening primrose oil provides about 200 mg of GLA. Intake of 600 to 3000 mg of GLA may bring about favorable results in the cancer patient.

AMINO ACIDS

Arginine.

Animals fed arginine rich diets (5%) had considerably fewer and more benign tumors when later treated with the carcinogen DMBA.²¹⁶

Arginine added to drinking water in animals was able to inhibit subcutaneous tumor growth.²¹⁷

Arginine added to diet of mice (5% of wt.) produced fewer tumors, slower growing tumors, and twice the mean survival time as compared to untreated mice.²¹⁸

Via animal studies, researchers have speculated on two primary functions of arginine in the body: essential for the synthesis of reparative collagen in wound recovery, decreases some of the negative aspects of metabolic responses to injury.²¹⁹

Arginine supplements in animals stimulated thymus activity which resulted in reduced tumor growth.²²⁰ Arginine also dramatically improves wound healing.

Arginine stimulates lymphocyte immune response in 21 healthy human volunteers.²²¹

Arginine supplements in tumor-bearing mice provided enhanced T-cell function, increased response to autologous tumors, retarded tumor growth, and prolonged median survival time.²²²

In mice with neuroblastomas, arginine supplements provided significant tumor retardation in the immunogenic group.²²³ Arginine's tumoricidal abilities go beyond its protein sparing abilities or immune stimulation.

Arginine supplements in mice provided significant enhancement of cytotoxic T-lymphocytes, natural killer cell activity, interleukin-2 receptors and general immune improvements.²²⁴

Toxicity. At therapeutic levels (above 5 grams/day) may activate growth of certain viruses.

n Branched chain amino acids (leucine, isoleucine, valine)

Accelerates protein synthesis and elevates albumin synthesis from 8.5% to 19.7% when used in TPN formula in 10 malnourished cancer patients.²²⁵

Cysteine (N-acetylcysteine)

Cysteine enters into various detoxification systems in the body. Can be converted to glutathione, which may become GSH, a potent broad spectrum anti-oxidant enzyme system. May reduce the toxicity of chemotherapeutic agents. N-acetylcysteine neutralizes a toxic by-product (acrolein) of cyclophosphamide therapy, hence preventing harm while allowing the effectiveness.²²⁶

N-acetylcysteine may neutralize the effectiveness of adriamycin while preventing the cardiotoxicity effects.²²⁷

N-acetylcysteine reduced the cardiotoxicity of doxorubicin in dogs.²²⁸

N-acetylcysteine blocked the cardiotoxicity of doxorubicin but did not affect the uptake or metabolism of the drug in the heart or liver.²²⁹

Acetylcysteine prevented the hemorrhagic cystitis that usually appears from ifosfamide administration.²³⁰

Topical application of N-acetylcysteine ointment may reduce toxic side effects (skin reactions, hair loss, damage to mucus membranes of the eyes) from radiation therapy.²³¹

Cysteine supplements promoted glutathione synthesis, which resulted in protection from the toxic effects of acetaminophen in mice.²³²

Toxicity. Although safe in dosages up to 10 grams/day, the nauseating taste and smell can cause vomiting. Normal dosage is 2-3 grams every 6 hours.

Methionine.

Methionine supplements reduced the uptake of mercury in test animals.²³³ This may help reduce the amount of toxins (chemotherapy) stored in healthy tissue.

OTHER NUTRIENT FACTORS

Green tea.

Tea catechins (tannins) are potent inhibitors of platelet aggregation in rabbit platelets.²³⁴

Green tea is a more potent scavenger of free radicals than vitamin C or E.²³⁵

Green tea contains potent anti-carcinogenic agents.²³⁶

Green tea was able to inhibit tumor initiation and promotion in animals.²³⁷


Maitake mushroom

Oral administration of maitake mushroom extract (Grifola frondosa) completely inhibited tumor growth in animals.²³⁸

Intraperitoneal injections of Maitake in tumor-induced animals showed an increase in cytostatic activity toward syngeneic tumor cells.²³⁹

Maitake supplements potentiated host-mediated antitumor activity in mice.²⁴⁰

Intraperitoneal injections of Maitake extract into tumor-induced animals showed marked inhibitory activity on the growth of solid form sarcoma.²⁴¹

n Plant phytosterols

Phytosterols in plants reduce the risk for colon cancer through a variety of factors.²⁴²

Plant carotenoids

A plant dormancy hormone and vitamin A analog (abscisic acid) showed profound anti-tumor activity in rats.²⁴³


Cartilage anti-angiogenesis factor

Inhibits tumor growth by preventing the tumor from developing an expanded circulatory network.²⁴⁴

Angiogenesis may be a key marker of tumor progression in 30 patients with malignancies and 19 without.²⁴⁵

There is an induction of angiogenesis during the transition from hyperplasia to neoplasia.²⁴⁶

A cartilage extract (Catrix) was able to markedly inhibit human tumor cell line growth from 22 different patients with malignancies.²⁴⁷

Extract of shark cartilage inhibited tumor growth in vivo.²⁴⁸

Infusion of cartilage extract markedly reduced tumor growth in animals.²⁴⁹

An isolated fraction of cartilage inhibited tumor neovascularization.²⁵⁰

Inhibition of vascularization via a factor in cartilage slows tumor growth.²⁵¹

Cartilage extract inhibits neo-vascularization (growth of new blood vessels).²⁵²

Catrix (preparation of bovine tracheal cartilage rings) was able to provide improvement in 90% of patients and complete remission in 61% of 31 cancer patients given first injections and then oral supplements (eight 375 mg caps every 8 hrs). There was no evidence of toxicity.²⁵³

An extract of shark cartilage was used to prevent tumor growth in implanted cornea tumors in rabbits.²⁵⁴ It could be that the extremely low incidence of tumors in sharks is due to the high presence of this cartilage anti-angiogenesis factor.

Calf scapular cartilage inhibited and reversed tumor growth for implanted tumors in rabbits and mice. No toxic effects were observed.²⁵⁵

Toxicity. No toxicity observed.

Glutamine.

May protect against enteritis resultant from radiation therapy.²⁵⁶

Alkylglycerols.

Highest sources are mother's milk, human bone marrow, and shark oil. Shown to enhance the regression of uterine cancer when administered prior to radiation therapy.²⁵⁷

Use of alkylglycerols prior to, during, and after radiation therapy reduced injuries by as much as two thirds.²⁵⁸

Coenzyme Q.

Reduces adverse side effects of chemotherapy with adriamycin, including cardiac output, anginal symptoms, and EKG abnormalities. Hair loss was also reduced.²⁵⁹

Cesium.

Neither an essential nor toxic mineral, cesium therapy is able to slightly alter the pH of the cancer cells to make them more vulnerable to immune attack.²⁶⁰


Maharishi-4 (an herbal preparation, ayurvedic food supplement)

Mice who were treated with M-4, then exposed to DMBA had reduced incidence and multiplicity of tumors. Those M-4 treated mice who did get cancer showed tumor regression in 60% of cases within 4 weeks.²⁶¹

Nucleic acids (RNA/DNA)

In protein depletion, RNA supplements may be mandatory in order to return immune functions to normal.²⁶²

ASSESSMENT

Fatty acids: serum fatty acid profile (both volumetric and germane ratios) are accurate indicators of metastatic progress.²⁶³ This test provides guidance for adjusting dietary fat intake, test available from Center for Human Functioning (316-682-3100) or Metametrix (800-221-4640).

Allergies: An overloaded immune system is compromised in its ability to destroy tumor cells. The debate continues on which is the best allergy test. ELISA/ACT measures immune delayed type hypersensitivity (Serammune 800-553-5472); Elisa measures IgE and IgG levels (Immuno Labs 800-231-9197).

Immune capability. Natural Killer cells are generally recognized as the most predictive aspect of the tumor killing capacity of the human immune system. Send blood sample to ImmunoSciences Lab (800-950-4686)

General diagnostics. Various tests at International Diagnostics (800-622-2343) or Metametrix

Vitamins (functional assay of enzymatic activity): by Metametrix (800-221-4640), or Pantox (619-272-3885), or Doctor's Data (800-323-2784)

C-strip: litmus paper dipped in fresh urine to indicate ascorbic acid content of blood (at or near saturation level) from Seraphim (800-525-7372)

Minerals: Provocative assay via chelating agent inducing urinary excretion. Volumetric and germane ratio recorded from Doctor's Data (800-323-2784)

Venous pH: Mild variations from normal indicate need for balancing using acid or alkaline diet.

Percent body fat by Futrex (800-545-1950) indicates serious long term lean tissue wasting or obesity that may accelerate tumor growth

Indirect calorimetry (INDC): Measures oxygen consumed and carbon dioxide exhaled to determine exact metabolic needs for calories. Essential test in cachectic TPN patients. Also called Metabolic Cart

Skin patch anergy test: indicates overall responsiveness of immune system

Oxidative stress: breath pentane as measured on gas chromatograph helps guide the balance between pro-oxidants (chemo & radiation) and anti-oxidants (nutrients)

Questionnaire: Quality of life indicators which help to track overall response from therapy.

Computer diet analysis: Helps educate patient on errant dietary habits by comparing patient's dietary intake with accepted standards of nutrient intake.

Digestion: Heidelberg capsule which is swallowed, then transmits the pH of the stomach and intestines to a nearby receiver (Heidelberg 404-449-4888)

Digestion, absorption, intestinal parasites: Send stool sample to appropriate labs.

References

1. Grant, JP, Proper use and recognized role of TPN in the cancer patient, Nutrition, vol.6, no.4, p.6S, July/Aug 1990 supplement

2. American College of Physicians, Parenteral Nutrition in Patients receiving cancer chemotherapy, Annals of Internal Medicine, vol.110, no.9, p.734, May 1989

3. Wilmore, DW, Catabolic illness, strategies for enhancing recovery, N. England J. Med., vol.325, no.10, p.695, Sept.1991

4. Bendich, A, and Chandra, RK (eds), MICRONUTRIENTS AND IMMUNE FUNCTIONS; CYTOKINES AND METABOLISM, New York Academy of Sciences, vol.587, 1990; see also Burns, JJ, et al. (eds), THIRD CONFERENCE ON VITAMIN C, New York Academy of Sciences, vol.498, 1987

5. Beisel, WR, Single nutrients and immunity, Amer. J. Clin. Nutr., vol.35, p.417, Feb.supplement 1987

6. Watson, RR, et al., Effect of beta-carotene on lymphocyte subpopulations in elderly humans: evidence for a dose response relationship, Amer. J. Clin. Nutr., vol.53, p.90, 1991

7. Weisburger, JH, American Journal Clinical Nutrition, vol.53, p.226S, 1991

8. Byers, T., et al., Patient Care, vol.11, p.34, 1990

9. Singh, VN, et al., American Journal Clinical Nutrition, vol.53, p.386S, 1991

10. Gouveia, J, et al., Lancet, no.1, p.710, 1982

11. Heimburger, DC, et al., Journal American Medical Association, vol.259, p.1525, 1988

12. Shklar, G., et al., European Journal Cancer Clinical Oncology, vol.24, no.5, p.839, 1988

13. DeCosse, JJ, et al., Journal National Cancer Institute, vol.81, p.1290, 1989

14. Prasad, KN, Journal American College of Nutrition, vol.9, no.1, p.28, 1990

15. Wargovich, MJ, et al., Gastroenterology, vol.103, p.92, July 1992

16. Kune, GA, et al., Nutrition & Cancer, vol.9, p.1, 1987

17. Good, RA, et al., Medical Oncology & Tumor Pharmacotherapy, vol.7, no.2, p.183, 1990

18. Simone, CB, CANCER & NUTRITION, Avery, Garden City, NY, 1992

19. Willett, WC, and MacMahon, B., New England Journal of Medicine, vol.310, p.633, Mar.8, 1984; and again p.697, Mar.15, 1984

20. Sakamoto, A, et al., in MODULATION AND MEDIATION OF CANCER BY VITAMINS, P.330, Karger, Basel Switzerland, 1983

21. Foster, HD, International Journal Biosocial Research, vol.10, no.1, p.17, 1988

22. Hoffer, A., et al., Journal Orthomolecular Medicine, vol.5, no.3, p.143, 1990

23. Axelrod, AE, and Traketelis, AC, Vitamins and Hormones, vol.22, p.591, 1964

24. Lowry, SF, et al., Surgical Forum, vol.28, p.143, 1977

25. Nichol, CA, Cancer Research, vol.29, p.2422, 1969

26. Norton, JA, et al., Cancer, vol.45, p.2934, 1980

27. Goodgame, JT, et al, American Journal Clinical Nutrition, vol.32, p.2277, Nov.1979

28. Goodgame, JT, et al., American Journal of Clinical Nutrition, vol.32, p.2277, 1979

29. Anthony, HM, et al., British Journal of Cancer, vol.46, p.354, 1982

30. Cheraskin, E., Journal of Alternative Medicine, p.18, Feb.1986

31. Hoffman, FA, Cancer, vol.55, 1 sup.1, p.295, Jan.1, 1985

32. Baker, H, et al., Journal American College Nutrition, vol.11, no.5, p.482, 1992

33. Hoffman, FA, Cancer, vol.55, p.295, 1985

34. Daly, JM, et al., Journal Parenteral and Enteral Nutrition, vol.14, no.5, p.244S, Sept.1990

35. Rennie, MJ, et al., Lancet, p.323, Feb.11, 1984

36. Flier, JS, et al., New England Journal Medicine, vol.325, no.10, p.695, Sept.1991

37. Dreizen, S., et al., Postgraduate Medicine, vol.87, no.1, p.163, Jan.1990

38. Dematrakopoulos, GE, and Brennan, MF, Cancer Research, (sup.),vol.42, p.756, Feb.1982

39. Annals of Internal Medicine, vol.110, no.9, p.735, May 1989

40. Kaminsky, M. (ed.), HYPERALIMENTATION: A GUIDE FOR CLINICIANS, Marcel Dekker, NY, Oct.1985

41. Dewys, WD, et al., American Journal of Medicine, vol.69, p.491, Oct.1980

42. Eys, JV, Cancer, vol.43, p.2030, 1979

43. Harvey, KB, et al., Cancer, vol.43, p.2065, 1979

44. Muller, JM, et al., Lancet, p.68, Jan.9, 1982

45. Norris, JR, et al., American Journal of Clinical Nutrition, vol.51, p.188, 1990

46. Gazzaniga, AB, et al., Archives of Surgery, vol. 123, p.1275, 1988

47. Abrahamian, V., et al., Journal of Parenteral and Enteral Nutrition, vol.7, no.5, p.465, 1983

48. Valdivieso, M., et al., Cancer Treatment Reports, vol.65, sup.5, p.145, 1981

49. Dewys, WD, et al., American Journal of Medicine, vol.69, p.491, Oct. 1980

50. Yam, D, Medical Hypothesis, vol.38, p.111, 1992

51. Demetrakopoulos, GE, et al., Cancer Research, vol.42, p.756S, Feb.1982

52. Rossi-Fanelli, F., et al., Journal Parenteral and Enteral Nutrition, vol.15, p.680, 1991

53. Bernstein, J., et al., American Journal Clinical Nutrition, vol.30, p.613, 1977

54. Nalder, BN, et al., Journal Nutrition, Apr.1972

55. Sanchez, A., et al., American Journal Clinical Nutrition, vol.26, p.180, 1973

56. Bristol, JB, et al., Proceedings American Association of Cancer Research, vol.26, p.206, Mar.1985

57. Horrobin, DF, Medical Hypotheses, vol.11, no.3, p.319, 1983

58. Hoehn, SK, et al., Nutrition & Cancer, vol.1, no.3, p.27, Spring 1979

59. Bendich, A., in BEYOND DEFICIENCY, New York Academy of Sciences, vol.669, p.300, 1992

60. Hathcock, JN, et al., in MICRONUTRIENTS AND IMMUNE FUNCTION, vol.587, p.257, New York Academy of Sciences, 1990

61. Meadows, GG, et al., American Journal of Clinical Nutrition, vol.54, p.1284S, 1991

62. Schmitt-Graff, A, et al., Pathology Research Practice, vol.181, no.2, p.168, 1986

63. Brown, RR, et al., Proceedings American Association Cancer Research, vol.22, p.184, 1981

64. Gupta, S., Progress in Clinical Biological Research, vol.259, p.307, 1988

65. Noto, V., et al., Cancer , vol.63, p.901, 1989

66. Shimpo, K, et al., American Journal Clinical Nutrition, vol.54, p.1298S, 1991

67. Ha, C, et al., Journal Nutrition, vol.114, p.938, 1984

68. Toma, S., et al., Cancer Detection and Prevention, vol.15, no.6, p.491, 1991

69. Ripoll, EA, et al., Journal Urology, vol.136, p.529, 1986

70. Prasad, KN, et al., Proceedings Society Experimental Biological Medicine, vol.164, no.2, p.158, 1980

71. Wood. L., New England Journal Medicine, vol.312, no.16, p.1060, 1985

72. Iakovkeva, SS, Arkh Patol, vol.42, no.9, p.93, 1980

73. Sundstrom, H., et al., Carcinogenesis, vol.10, p.273, 1989

74. Kochi, M., et al., Progress in Cancer Research and Therapy, vol.35, p.338, 1988

75. Leihr, JG, American Journal Clinical Nutrition, vol.54, p.1256S, 1991

76. Coudray, C, et al., Basic Research in Cardiology, vol.87, p.173, 1992

77. Kimie, S, et al., Japanese Journal Cancer Research, vol.83, p.45, Jan.1992

78. Horsman, MR, Radiotherapy & Oncology, vol.22, p.79, 1991

79. Wadleigh, RG, et al., American Journal Medicine, vol.92, p.481, May 1992

80. Shimpo, K., et al., American Journal Clinical Nutrition, vol.54, p.1298S, 1991

81. Baute, L., Journal National Cancer Institute, vol.83, no.22, p.1614, Nov.20, 1991

82. Alexander, JW, et al., Critical Care Medicine, vol.18, p.S159, 1990

83. Rhodes, J., and Oliver, S., Immunology, vol.40, p.467, 1980

84. Talbott, MC, et al., American Journal of Clinical Nutrition, vol.46, p.659, 1987

85. Bendich, A., et al., Journal of Nutrition, vol.116, p.675, 1986

86. Cerutti, PA, Science, vol.227, p.375, 1985

87. Boyd, JN, et al., Food Chemistry and Toxicology, vol.20, p.47, 1982

88. Quillin, P., SAFE EATING, p.129, M.Evans, NY, 1990

89. Shklar, G., et al., Journal of the National Cancer Institute, vol.78, no.5, p.987, May 1987

90. Cook, MG, and McNamara, P., Cancer Research, vol.40, p.1329, Apr.1980

91. Trickler, D., and Shklar, G., Journal of the National Cancer Institute, vol.78, no.1, p.165, Jan.1987

92. Prasad, KN, et al., Proceedings of the Society for Experimental Biology and Medicine, vol.164, p.158, 1980

93. Journal of the American Medical Association, vol.244, no.10, p.1077, Sept.5, 1980

94. Panganamala, RV, and Cornwell, DG, Annals of NY Academy of Sciences, vol.393, p.376, 1982

95. Myers, CE, et al., Annals of NY Academy of Sciences, vol.393, p.419, 1982

96. Horvath, HM, and Ip, C., Cancer Research, vol.43, p.5335, Nov.1983

97. Van Vleet, JF, and Ferrans, VJ, Cancer Treatment Reports, vol.64, p.315, 1980

98. Singal, PK, and Tong, J., Molecular and Cellular Biochemistry, vol.84, p.163, 1988

99. Ripoll, EA, et al., Journal of Urology, vol.136, p.529, 1986

100. Prasad, KN, et al., Cancer Research, vol.42, p.550, Feb.1982

101. Svingen, BA, et al., Cancer Research, vol.41, p.3395, Sept.1981

102. Shklar, G., and Schwartz, J., European Journal of Cancer Clinical Oncology, vol.24, no.5, p.839, 1988

103. Wang, YM, et al., MOLECULAR INTERRELATIONS OF NUTRITION AND CANCER, Arnott, MS (eds.), Raven Press, NY, 1982

104. Waxman, S., and Bruckner, H., European Journal of Cancer and Clinical Oncology, vol.18, no.7, p.685, 1982

105. Kagerud, A., et al., Oncology, vol.20, p.1, 1981

106. Kagerud, A., and Peterson, H., Anticancer Research, vol.1, p.35, 1981

107. Traber, MG, et al., New England Journal of Medicine, vol.317, p.262, 1987

108. Nutrition Reviews, vol.45, no.1, p.27, Jan.1987

109. Milei, J., et al., American Heart Journal, vol.111, p.95, 1986

110. Wang, YM, et al., Cancer Research, vol.40, p.1022, Apr.1980

111. Wood, LA, New England Journal of Medicine, Apr.18, 1985

112. Bendich, A., and Machlin, LJ, American Journal of Clinical Nutrition, vol.48, p.612, 1988

113. Suttie, JW, HANDBOOK OF VITAMINS, Machlin (ed.), Marcel Dekker Publ., NY, p.146, 1991

114. National Academy of Sciences, RECOMMENDED DIETARY ALLOWANCES, National Academy Press, p.69, 1980

115. Chlebowski, RT, et al., Cancer Treatment Reviews, vol.12, p.49, 1985

116. Dreizen, S., Postgraduate Medicine, vol.87, no.1, p.167, Jan.1990

117. Conly, J., et al, American Journal of Clinical Nutrition, vol.50, p.109, 1989

118. March, BE, et al., Journal of Nutrition, vol.103, p.371, 1973

119. Krishnamurthi, S., et al., Radiology, vol.99, p.409, 1971

120. Long, JW, ESSENTIAL GUIDE TO PRESCRIPTION DRUGS, Harper & Row, NY, p.790, 1982

121. Poydock, ME, American Journal Clinical Nutrition, vol.54, p.1261S, 1991

122. Taper, HS, et al., International Journal of Cancer, vol.40, no.4, p.575, Oct.15, 1987

123. Crary, EJ, et al., Medical Hypotheses, vol.13, p.77, 1984

124. Sakamoto, A., et al., in MODULATION AND MEDIATION OF CANCER BY VITAMINS, p.330, Karger, Basel, 1983

125. Taper, HS, et al., International Journal of Cancer, vol.40, p.575, 1987

126. Sprince, H., et al., Agents and Actions, vol.5, no.2, p.164, 1975

127. Cameron, E., and Pauling, L., Proceedings of the National Academy of Sciences USA, vol.75, no.9, p.4538, Sept.1978

128. Kawai-Kobayashi, K., et al., Journal of Nutrition, vol.116, p.98, 1986

129. Anderson, R., et al., American Journal of Clinical Nutrition, vol.33, p.71, 1980

130. Bussey, JR, et al., Cancer, vol.50, p.1434, 1982

131. Tschetter, L., et al., Proceedings of the American Society of Clinical Oncology, vol.2, p.92, 1983

132. Poydock, E., IRCS Medical Science, vol.12, p.813, 1984

133. Kim, JH, et al., Cancer Research, vol.44, p.102, Jan.1984

134. Verma, AK, et al., Cancer Research, vol.48, p.5754, Oct.1988

135. Castillo, MH, et al., American Journal Surgery, vol.158, p.351, Oct.1989

136. LeBon, AM, et al., Chemical Biological Interactions, vol.83, p.65, 1992

137. Michalek, AM, et al., Nutrition and Cancer, vol.9, p.143, 1987

138. Micksche, M., et al., Oncology, vol.34, p.234, 1977

139. Kurata, T., and Micksche, M., International Journal of Cancer Research and Treatment, vol.34, no.5, p.1, 1977

140. Levenson, SM, et al., Annals of Surgery, vol.200, no.4, p.494, Oct.1984

141. Band, PR, et al., Preventive Medicine, vol.13, p.549, 1984

142. Pastorino, E., et al., Oncology, vol.48, p.131, 1991

143. Bendich, A., and Langseth, L., American Journal of Clinical Nutrition, vol.49, p.358, 1989

144. Bendich, A., American Journal Clinical Nutrition, vol.49, p.358, 1989

145. Bendich, A., Journal of Nutrition, vol.119, p.112, 1989

146. Burton, GW, Journal of Nutrition, vol.119, p.109, 1989

147. Bond, GG, et al., Nutrition and Cancer, vol.9, p.109, 1987

148. Bendich, A., Clinical Nutrition, vol.7, p.113, 1988

149. Krinsky, NI, Journal of Nutrition, vol.119, p.123, 1989

150. Schwartz, J., et al., Journal of Oral Maxillofacial Surgery, vol.45, p.510, 1987

151. Bendich, A., Nutrition and Cancer, vol.11, p.207, 1988

152. Costantino, JP, et al., American Journal of Clinical Nutrition, vol.48, p.1277, 1988

153. Bischoff, F., et al., Archives Pathology, vol.35, p.713, 1943

154. Tryfiates, GP, et al., Anticancer Research, vol.1, p.263, 1981

155. DiSorbo, DM, et al., Nutrition and Cancer, vol.5, no.1, p.10, 1983

156. DiSorbo, DM, et al., Nutrition & Cancer, vol.7, p.43, 1985

157. Gridley, DS, et al., Nutrition Research, vol.8, p.201, 1988

158. Byar, D. et al., Urology, vol.10, no.6, p.556, Dec.1977

159. DiSorbo, DM, et al., Nutrition and Cancer, vol.3, no.4, p.216, 1982

160. DiSorbo, DM, et al., Nutrition and Cancer, vol.7, p.43, 1985

161. Ladner, HA, et al., in VITAMINS AND CANCER, Meyskens, FL, (eds.), p.429, Humana Press, Clifton, NJ, 1986

162. Stone, OJ, Medical Hypotheses, vol.30, p.277, 1989

163. Pais, RC, et al., Cancer, vol.66, p.2421, 1990

164. DiSorbo, DM, et al., Nutrition and Cancer, vol.5, no.1, p.10, 1983

165. Shultz, TD, et al., Anticancer Research, vol.8, p.1313, 1988

166. Ladner, HA, et al., Nutrition, Growth, & Cancer, p.273, Alan Liss, Inc., 1988

167. Cohen, M., and Bendich, A., Toxicology Letters, vol.34, p.129, 1986

168. Watrach, AM, et al., Cancer Letters, vol.25, p.41, 1984

169. Ip, C., and Sinha, D., Carcinogenesis, vol.2, no.5, p.435, 1981

170. Davies, MH, et al., Drug Nutrition Interactions, vol.5, p.169, 1987

171. Nutrition Reviews, vol.42, no.7, p.260, July 1984

172. Ip, C., Cancer Research, vol.41, p.4386, Nov.1981

173. Lawson, T., and Birt, DF, Chemical Biological Interactions, vol.45, p.95, 1983

174. Milner, JA, and Hsu, CY, Cancer Research, vol.41, p.1652, May 1981

175. Greeder, GA, and Milner, JA, Science, vol.209, p.825, Aug.1980

176. Ohkawa, K., et al., British Journal of Cancer, vol.58, p.38, 1988

177. Petrie, HT, et al., Journal of Leukocyte Biology, vol.45, p.215, 1989

178. Dharwadkar, SM, et al., Nutrition and Cancer, vol.10, p.163, 1987

179. Karmali, RA, et al., Journal of the National Cancer Institute, vol.73, p.457, 1984

180. Sakaguchi, M., et al., British Journal of Cancer, vol.62, p.742, Nov.1990

181. Szeluga, DJ, et al., American Journal of Clinical Nutrition, vol.45, p.859, 1987

182. Blank, EW, et al., Journal of Steroid Biochemistry, vol.34, p.149, 1989

183. Karmali, RA, Journal of Internal Medicine (suppl), vol.225, p.197, 1989

184. Karmali, RA, Preventive Medicine, vol.16, p.493, July 1987

185. O'Connor, TP, et al., Journal of the National Cancer Institute, vol.75. p. 959, Nov. 1985

186. Braden, LM, et al., Lipids, vol.21, p.285, 1986

187. Karmali, RA, et al., Journal of the National Cancer Institute, vol.73, p.457, 1984

188. Gabor, H., et al., Journal of the National Cancer Institute, vol.76, p. 1223, 1986

189. Kort, WJ, et al., Carcinogenesis, vol.8, p.611, 1987

190. Pritchard, GA, et al., British Journal of Surgery, vol.76, p.1069, 1989

191. Borgeson, CE, et al., Lipids, vol.24, p. 290, 1989

192. Cannizzo, F., et al., Cancer Research, vol.49, p.3961, 1981

193. Roebuck, BD, et al., Cancer Research, vol.41, p.3961, 1981

194. O'Connor, TP, et al., Journal of the National Cancer Institute, vol.81, p.858, 1989

195. Karmali, RA, et al., Anticancer Research, vol.7, p.1173, 1987

196. Rose, DP, et al., Carcinogenesis, vol.9, p.603, 1988

197. Adams, L., et al., Proceedings of the American Association of Cancer, vol.28, p.159, 1987

198. Burns, CP, et al., Nutrition Reviews, vol.48, p.233, June 1990

199. Guffy, MM, et al., Cancer Research, vol.44, p.1863, 1984

200. Reich, R., et al., Biochemical and Biophysical Research Communication, vol.160, p.559, 1989

201. Begin, ME, et al., Prostaglandins, Leukotriennes, and Medicine, vol.19, p.177, Aug.1985

202. Begin, ME, et al., Anticancer Research, vol.6, p.291, 1986

203. Begin, ME, et al, Journal of the National Cancer Institute, vol.77, p.1053, 1986

204. Booyens, J., et al., IRCS Medical Science, vol. 14, p.396, 1986

205. Zijlstra, JG, et al., International Journal of Cancer, vol.40, p.850, 1987

206. Osborne, MP, et al., Cancer Investigation, vol.6, p.629, 1988

207. Wan, JM, et al., Federation of the American Society for Experimental Biology, vol.A350, p.21, 1988

208. Wan, JM, et al., World Review of Nutrition and Dietetics, vol.66, p.477, 1991

209. Mascioli, EA, et al., Lipids, vol.23, p.623, 1988

210. Mascioli, EA, et al., American Journal of Clinical Nutrition, vol.49, p.277, 1989

211. Pomposelli, JJ, et al., Journal of Parenteral and Enteral Nutrition, vol.13, p.136, 1989

212. van der Merwe, CF, South African Medical Journal, vol.65, p.712, 1984

213. van der Merwe, CF, et al., British Journal of Clinical Practice, vol.41, no.9, p.907, 1987

214. Takeda, S., et al., Anticancer Research, vol.12, p.329, 1992

215. Begin, ME, et al., Journal National Cancer Institute, vol.77, p.1053, 1986

216. Takeda, Y., et al., Cancer Research, vol. 35, p.2390, Sept.1975

217. Pryme, IF, Cancer Letters, vol.5, p.19, 1978

218. Milner, JA, et al., Journal of Nutrition, vol.109, p.489, 1979

219. Seifter, E., et al., Surgery, vol.84, no.2, p.224, 1978

220. Critselis, AN, et al., Federation Proceedings, vol.36, p.1163, 1977

221. Barbul, A., et al., Surgery, vol.90, no.2, p.244, 1981

222. Reynolds, JV, et al., Annals of Surgery, p.202, Feb.1990

223. Reynolds, JV, et al., Journal of Surgical Research, vol.45, p.513, 1988

224. Reynolds, JV, et al., Surgery, vol.104, no.2, p.142, Aug.1988

225. Tayek, JA, et al., Clinical Research, vol.33, no.1, p.72A, 1985

226. Palermo, MS, et al., International Journal of Immunopharmacology, vol.8, no.6, p.651, 1986

227. Schmitt-Graff, A., and Scheulen, ME, Pathology Resident Practice, vol.181, no.2, p.168, 1986

228. Morgan, LR, et al., Seminars in Oncology, vol.10, 1 sup.1, p.56, 1983

229. Doroshow, JH, et al., Journal of Clinical Investigation, vol.68, no.4, p.1053, 1981

230. Watson, RA, Urology, vol.24, no.5, p.465, 1984

231. Kim, JA, et al., Seminars in Oncology, vol.10, 1 sup.1, p.86, 1983

232. Williamson, JM, et al., Proceedings of the National Academy of Sciences, vol.79, p.6246, Oct.1982

233. Meydani, Mohsen, and Mathcock, JN, Drug-Nutrient Interactions, vol.2, p.217, 1984

234. Mitane, Y., et al., Chemical Pharmaceutical Bulletin, vol.38, no.3, p.790, 1990

235. Zhao, B., et al., Cell Biophysics, vol.14, p.175, 1989

236. Wang, ZY, et al., Drug Metabolism & Disposition, vol.16, no.1, p.98, 1988

237. Katiyar, SK, et al., Nutrition and Cancer, vol.18, p.73, 1992

238. Hishida, I., et al., Chemical Pharmaceutical Bulletin, vol.36, no.5, p.1819, 1988

239. Adachi, Y, et al., Journal Pharmacobiodynamics, vol.10, no.11, p.644, Nov.1987

240. Adachi, K, et al., Chemical Pharmacological Bulletin, vol.35, no.1, p.262, Jan.1987

241. Ohno, N, et al., Journal Pharmacobiodynamics, vol.9, no.10, p.861, Oct.1986

242. Rao, AV, et al., Nutrition and Cancer, vol.18, p.43, 1992

243. Shearer, RW, Modulation and Mediation of Cancer by Vitamins, p.89, Karger, Basel, 1983

244. Folkman, J., et al., Nature, vol.339, p.58, 1989; see also Langer, R., et al., Science, vol.193, p.70, 1976

245. Weidner, N., et al., New England Journal of Medicine, vol.324, no.1, p.1, 1991

246. Folkman, J, et al., Nature, vol.339, p.58, May 1989

247. Durie, BG, et al., Journal of Biological Response Modifiers, vol.4, p.590, 1985

248. Oikawa, T., et al., Cancer Letters, vol.51, p.181, 1990

249. Langer, R., et al., Proceedings National Academy Science, vol.77, no.7, p.4331, July 1980

250. Langer, R. et al, Science, p.70, July 1976

251. D'Amore, PA, Seminars in Thrombosis and hemostasis, vol.14, no.1, p.73, 1988

252. Moses, MA, et al., Science, vol.248, p.1408, June 1990

253. Prudden, JF, Journal of Biological Response Modifiers, vol.4, no.6, p.551, 1985

254. Langer, R., and Lee, A., Science, vol.221, p.1185, 1983

255. Langer, R., and Murray, J., Journal of Applied Biochemical Biotechnology, vol.8, no.9, p.1983; see also Langer, R., et al., Proceedings of the National Academy of Science USA, vol.77, p.4331, 1980; see also, Luer, CA, Federation Proceedings, vol.45, p.949, 1986

256. Klimberg, S., presentation to the annual meeting of Society of Surgical Oncology and American Society of Clinical Oncology, San Francisco, 1989

257. Brohult, A., et al., Acta Obstetric Gynecologica Scandinavica, vol.65, no.7, p.779, 1986

258. Brohult, A., et al., Acta Obstetric Gynecologica Scandinavica, vol.58, no.2, p.203, 1979

259. Werbach, M., NUTRITIONAL INFLUENCES ON ILLNESS, Third Line Press, Tarzana, CA 1988

260. Sartori, HE, Pharmacology, Biochemistry, & Behavior, vol.21, sup.1, p.7, 1984

261. Sharma, HM, et al., Pharmacology Biochemistry and Behavior, vol.35, p.767, 1990

262. Pizzini, RP, et al., Surgical Infection Society abstract, p.50, 1989

263. Wood, B, et al., European Journal of Surgical Oncology, vol.11, p.347, 1985; see also Wood, B., et al., British Medical Journal, vol.291, p.163, July 1986

Molybdenum for breast cancer:

 

Zhonghua Zhong Liu Za Zhi 1987 May;9(3):204-7

[Effect of molybdenum and tungsten on mammary carcinogenesis in Sprague-Dawley (SD) rats]

[Article in Chinese]

Wei HJ, Luo XM, Yang XP.

Cancer Institute, Chinese Academy of Medical Sciences, Beijing.

Virgin female rats of SD strain were given ad libitum a nutritionally adequate semipurified diet containing 0.026 ppm molybdenum and deionized water (groups 1-3) or the same diet with 150 ppm tungsten and the drinking water (group 4). Group 1 was used as control. After 15 days, all the animals in groups 2-4 received an intravenous injection of N-nitroso-N-methylurea (NMU) 5 mg/100 g body weight. One week after administration of carcinogen, 10 ppm Mo was added to the drinking water in group 3. After 125 days, the mammary cancer incidence in group 4 (79.2%) was significantly higher than that in group 2 (50.0%) or group 3 (45.5%) (P less than 0.05). After 198 days, the average number of mammary cancer in each animal and mammary cancer incidence in group 3 (1.5 and 50.0%) were obviously lower than those in group 2 (2.0 and 90.5%) or group 4 (2.6 and 95.7%). The first palpable mammary tumor was found in the W-supplemented group only 56 days after the injection of NMU, whereas in the W-unsupplemented and Mo-supplemented groups, the first mammary tumor was observed 71 and 85 days after NMU treatment. Of these 181 mammary tumors, 177 (97.8%) were adenocarcinoma or papillary carcinoma, only 4 (2.2%) fibroadenocarcinoma. The results of this study show, for the first time, the inhibitory effect of Mo on the mammary carcinogenesis and promoting effect of Tungsten, an antagonist of molybdenum, on the tumor growth.