The field of investigation of the role of nutrition in the cancer process is very broad. It is becoming clearer as research continues that nutrition plays a major role in cancer. It has been estimated by the American Institute for Cancer Research and the World Cancer Research Fund that 30–40 percent of all cancers can be prevented by appropriate diets, physical activity, and maintenance of appropriate body weight 1. It is likely to be higher than this for some individual cancers.

Most of the research on nutrition and cancer has been reductionist; that is, a particular food or a nutrient has been studied in relation to its impact on tumor formation/regression or some other end point of cancer at a particular site in the body. These studies are very helpful in seeing the details of the mechanisms of disease. However, they do not help give an overall picture of how to prevent cancer on a dietary level. Even less, they tell little of how to eat when a person already has a cancer and would like to eat a diet that is favorable to their recovery.

This review will focus on those dietary factors which has been shown to be contribute to increased risk of cancer and then on those additional protective dietary factors which reduce cancer risk. Finally, some whole-diet studies will be mentioned which give a more complete picture of how these individual factors work together to reduce cancer risk.

Eating too much food is one of the main risk factors for cancer. This can be shown two ways: (1) by the additional risks of malignancies caused by obesity, and (2) by the protective effect of eating less food.

Obesity has reached epidemic proportions in the United States. Sixty-four percent of the adult population is overweight or obese 2. About 1 in 50 are now severely obese (BMI > 40 kg/m2) 3. Mokdad et al 4 found that poor diet and physical inactivity was the second leading cause of death (400,000 per year in the USA), and would likely overtake tobacco as the leading cause of death.

It was estimated in a recent study, from a prospective cancer prevention cohort, that overweight and obesity accounted for 14 percent of all cancer deaths in men and 20 percent of those in women 5. Significant positive associations were found between obesity and higher death rates for the following cancers: esophagus, colon and rectum, liver, gallbladder, pancreas, kidney, stomach (in men), prostate, breast, uterus, cervix, and ovary 5. The authors estimated that over 90,000 cancer deaths per year could be avoided if the adult population all maintained a normal weight (BMI < 25.0) 5. Clearly, obesity is a major risk factor for cancer.

On the other side, careful menu planning brings about an approach entitled CRON-Calorie Restriction with Optimal Nutrition. The basic idea is to eat a reduced amount of food (about 70–80 percent of the amount required to maintain "normal" body weight) while still consuming all of the necessary amounts of vitamins, minerals, and other necessary nutrients. The only restriction is the total amount of energy (calories) that is consumed. While being difficult to practice, this approach has a lot of scientific merit for being able to extend average life spans of many species of animals including rats, mice, fish, and possibly primates (currently being tested). Along with this life span extension is a reduction in chronic diseases that are common to mankind, reviewed in Hursting et al 6. A recent meta-analysis of 14 experimental studies found that energy restriction resulted in a 55% reduction in spontaneous tumors in laboratory mice 7. Calorie restriction inhibited induced mammary tumors in mice 8 and suppressed implanted tumor growth and prolonged survival in energy restricted mice 9. Among Swedish women who had been hospitalized for anorexia nervosa (definitely lower caloric intake, but not adequate nutrition) prior to age 40, there was a 23% lower incidence of breast cancer for nulliparous women and a 76% lower incidence for parous women 10. So, too many calories is definitely counter-productive, and slightly less than normal is very advantageous.

Refined sugar is a high energy, low nutrient food – junk food. "Unrefined" sugar (honey, evaporated cane juice, etc) is also very concentrated and is likely to contribute to the same problems as refined sugar. Refined wheat flour products are lacking the wheat germ and bran, so they have 78 percent less fiber, an average of 74 percent less of the B vitamins and vitamin E, and 69 percent less of the minerals (USDA Food database, data not shown). Concentrated sugars and refined flour products make up a large portion of the carbohydrate intake in the average American diet. One way to measure the impact of these foods on the body is through the glycemic index.

The glycemic index is an indication of the blood sugar response of the body to a standardized amount of carbohydrate in a food. The glycemic load takes into account the amount of food eaten. An international table of the glycemic index and glycemic load of a wide variety of foods has been published 11.

Case-control studies and prospective population studies have tested the hypothesis that there is an association between a diet with a high glycemic load and cancer. The case control studies have found consistent increased risk of a high glycemic load with gastric 12, upper aero digestive tract 13, endometrial 14, ovarian 15, colon or colorectal cancers 1617. The prospective studies' results have been mixed. Some studies showed increased risk of cancer in the whole cohort with high glycemic load 181920; some studies found only increased risk among subgroups such as sedentary, overweight subjects 21222324; other studies concluded that there was no increased risk for any of their cohort 25262728. Even though there were no associations between glycemic load and colorectal, breast, or pancreatic cancer in the Nurses' Health Study there was still a strong link between diabetes and colorectal cancer 29.

Perhaps the dietary glycemic load is not consistently related to glucose disposal and insulin metabolism due to individual's different responses to the same glycemic load. Glycated hemoglobin (HbA_1c) is a time-integrated measurement of glucose control, and indirectly, of insulin levels. Increased risk in colorectal cancer was seen in the EPIC-Norfolk study with increasing HbA_1c; subjects with known diabetes had a three-fold increased risk of colorectal cancer 30. In a study of a cohort in Washington county, Maryland, increased risk of colorectal cancer was seen in subjects with elevated HbA_1c, BMI > 30 kg/m², or who used medications to control diabetes 31. However, glycated hemoglobin was not found to be associated with increased risk of colorectal cancer in a small nested case-control study within the Nurses' Health Study 32. Elevated fasting glucose, fasting insulin, 2 hour levels of glucose and insulin after an oral glucose challenge, and larger waist circumference were associated with a higher risk of colorectal cancer 33. In multiple studies diabetes has been linked with increased risk of colorectal cancer 34353637, endometrial cancer 38, and pancreatic cancer 3539. It is clear that severe dysregulation of glucose metabolism is a risk factor for cancer. Foods which contribute to hyperinsulinemia, such as refined sugar, foods containing refined sugar, and refined flour products should be avoided and eliminated from a cancer protective diet.

Unrefined plant foods typically have an abundance of fiber. Dairy products, eggs, and meat all have this in common – they contain no fiber. Refined grain products also have most of the dietary fiber removed from them. So, a diet high in animal products and refined grains (a typical diet in the USA) is low in fiber. In prospective health studies low fiber was not found to be a risk for breast cancer 25. It is possible that fiber measurements are just a surrogate measure for unrefined plant food intake. Slattery et al 40 found an inverse correlation between vegetable, fruit and whole grain intake plant food intake and rectal cancer, while refined grains were associated with increased risk of rectal cancer. A threshold of about 5 daily servings of vegetables was needed to reduce cancer risk and the effect was stronger among older subjects 40. Many other nutrients are co-variants with fiber, including folic acid, which is covered in detail below.

Red meat has been implicated in colon and rectal cancer. A Medline search in February 2003 uncovered 26 reports of human studies investigating the link between diet and colon or colorectal cancer. Of the 26 reports, 21 of them reported a significant positive relationship between red meat and colon or colorectal cancer 17414243444546474849505152535455565758596061626364. A recent meta-analysis also found red meat, and processed meat, to be significantly associated with colorectal cancer 65. Meat, and the heterocyclic amines formed in cooking, have been correlated to breast cancer in a case-control study in Uruguay as well 66.

Omega 3 fats (alpha-linolenic acid, EPA, DHA) have been shown in animal studies to be protect from cancer, while omega 6 fats (linoleic acid, arachidonic acid) have been found to be cancer promoting fats. Now there have been several studies that have tested this hypothesis in relation to breast cancer, summarized in Table 1. Except for the study by London et al 67, all of these studies found an association between a higher ratio of N-3 to N-6 fats and reduced risk of breast cancer. Long chain N-3 and N-6 fats have a different effect on the breast tumor suppressor genes BRCA1 and BRCA2. Treatment of breast cell cultures with N-3 fats (EPA or DHA) results in increased expression of these genes while arachadonic acid had no effect 68. Flax seed oil and DHA (from an algae source) both can be used to increase the intake of N-3 fat, with DHA being a more efficient, sure source.

Flax seed provides all of the nutrients from this small brown or golden hard-coated seed. It is an excellent source of dietary fiber, omega 3 fat (as alpha-linolenic acid), and lignans. The lignans in flax seed are metabolized in the digestive tract to enterodiol and enterolactone, which have estrogenic activity. In fact, flax seed is a more potent source of phytoestrogens than soy products, as flax seed intake caused a bigger change in the excretion of 2-hydroxyestrone compared to soy protein 69.

Ground flax seeds have been studied for its effect on cancer, including several excellent studies by Lilian Thompson's research group at the University of Toronto. In one study the flax seed, its lignan fraction, or the oil were added to the diet of mice who had previously been administered a chemical carcinogen to induce cancer. All three treatments reduced the established tumor load; the lignan fraction containing secoisolariciresinol diglycoside (SDG) and the flax seed also reduced metastasis 70. In another study the flax lignan SDG was fed to mice starting 1 week after treatment with the carcinogen dimethylbenzanthracene. The number of tumors per rat was reduced by 46% compared to the control in this study 71. Flax or its lignan (SDG) were tested to see if they would prevent melanoma metastasis. The flax or lignan fraction were fed to mice two weeks before and after injection of melanoma cells. The flax treatment (at 2.5, 5, or 10% of diet intake) resulted in a 32, 54, and 63 percent reduction in the number of tumors, compared to the control 72. The SDG, fed at amounts equivalent to the amount in 2.5, 5, or 10% flax seed, also reduced the tumor number, from a median number of 62 in the control group to 38, 36, and 29 tumors per mouse in the SDG groups, respectively 73.

More recently Thompson's research group studied mice that were injected with human breast cancer cells. After the injection the mice were fed a basal diet (lab mouse chow) for 8 weeks while the tumors grew. Then one group continued the basal diet and another was fed a 10% flax seed diet. The flax seed reduced the tumor growth rate and reduced metastasis by 45% 74.

Flax seed has been shown to enhance mammary gland morphogenesis or differentiation in mice. Nursing dams were fed the 10% flax seed diet (or an equivalent amount of SDG). After weaning the offspring mice were fed a regular mouse chow diet. Researchers then examined the female offspring and found an increased number of terminal end buds and terminal ducts in their mammary glands with more epithelial cell proliferation, all demonstrating that mammary gland differentiation was enhanced 75. When these female offspring were challenged with a carcinogen to induce mammary gland tumors there were significantly lower incidence of tumors (31% and 42% lower in the flax seed and SDG groups, respectively), significantly lower tumor load (51% and 62% lower in the flax seed and SDG groups, respectively), significantly lower mean tumor size (44% and 68% lower in the flax seed and SDG groups, respectively), and significantly lower tumor number (47% and 45% lower in the flax seed and SDG groups, respectively) 76. So, flax seed and its lignan were able to reduce tumor growth (both in number and size of tumors), prevent metastasis, and even cause increased differentiation of mouse mammary tissue in suckling mice, making the offspring less susceptible to carcinogenesis even when not consuming any flax products.

Other researchers have tested flax seed and prostate cancer. In an animal model using mice, Lin et al 77 found that a diet supplemented with 5% flax inhibited the growth and development of prostate cancer in their experimental mouse model. A pilot study of 25 men who were scheduled for prostatectomy surgery were instructed to eat a low-fat diet (20% or less of energy intake) and to supplement with 30 g of ground flaxseed per day. During the follow-up of an average of 34 days there were significant changes in serum cholesterol, total testosterone, and the free androgen index 78. The mean proliferation index of the experimental group was significantly lower and apoptotic indexes higher compared to historical matched controls. Ground flax seed may be a very beneficial food for men battling prostate cancer. However, a meta-analysis of nine cohort and case-control studies revealed an association between flax seed oil intake or high blood levels of alpha-linolenic acid and prostate cancer risk 79. It is quite likely that the lignans in flax seed are a major component of flax's anti-cancer effects so that flax oil without the lignans is not very beneficial. Some brands of flax seed oil retain some of the seed particulate because of the beneficial properties of the lignans.

One of the most important messages of modern nutrition research is that a diet rich in fruits and vegetables protects against cancer. (The greatest message is that this same diet protects against almost all other diseases, too, including cardiovascular disease and diabetes.) There are many mechanisms by which fruits and vegetables are protective, and an enormous body of research supports the recommendation for people to eat more fruits and vegetables.

Block et al 80 reviewed about 200 studies of cancer and fruit and vegetable intake. A statistically significant protective effect of fruits and vegetables was found in 128 of 156 studies that gave relative risks. For most cancers, people in the lower quartile (1/4 of the population) who ate the least amount of fruits and vegetables had about twice the risk of cancer compared to those who in the upper quartile who ate the most fruits and vegetables. Even in lung cancer, after accounting for smoking, increasing fruits and vegetables reduces lung cancer; an additional 20 to 33 percent reduction in lung cancers is estimated 1.

Steinmetz and Potter reviewed the relationship between fruits, vegetables, and cancer in 206 human epidemiologic studies and 22 animal studies 81. They found "the evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon." Vegetables, and particularly raw vegetables, were found to be protective; 85% of the studies that queried raw vegetable consumption found a protective effect. Allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes also had a fairly consistent protective effect 81. Allium vegetables (garlic, onion, leeks, and scallions) are particularly potent and have separately been found to be protective for stomach and colorectal cancers 8283 and prostate cancer 84.

There are many substances that are protective in fruits and vegetables, so that the entire effect is not very likely to be due to any single nutrient or phytochemical. Steinmetz and Potter list possible protective elements: dithiolthiones, isothiocyanates, indole-32-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene (and other carotenoids), lycopene, selenium, vitamin E, flavonoids, and dietary fiber 81.

A joint report by the World Cancer Research Fund and the American Institute for Cancer Research found convincing evidence that a high fruit and vegetable diet would reduce cancers of the mouth and pharynx, esophagus, lung, stomach, and colon and rectum; evidence of probable risk reduction was found for cancers of the larynx, pancreas, breast, and bladder 1.

Many of the recent reports from prospective population-based studies of diet and cancer have not found the same protective effects of fruits and vegetables that were reported earlier in the epidemiological and case-control studies [reviewed in 85]. One explanation is that people's memory of what they ate in a case-cohort study may have been tainted by their disease state. Another problem might be that the food frequency questionnaires (FFQ) used to measure food intake might not be accurate enough to detect differences. Such a problem was noted in the EPIC study at the Norfolk, UK site. Using a food diary the researchers found a significant correlation between saturated fat intake and breast cancer, but using a FFQ there was no significant correlation 86. So, inaccurate measurement of fruit and vegetable intake might be part of the explanation as well.

It must be noted that upper intakes of fruits and vegetables in these studies are usually within the range of what people on an American omnivorous diet normally eat. In the Nurses Health Study the upper quintiles of fruit and vegetable intake were 4.5 and 6.2 servings/day, respectively 87. Similarly, the upper quintiles of fruit and vegetable intake in the Health Professionals Follow-up Study were 4.3 and 5.4 serving/day for fruits and vegetables, respectively 87. Intakes of fruits and vegetables on the Hallelujah Diet are much higher, with median reported intakes of six servings of fruits (646 g/day) and eleven servings of vegetables per day (971 g/day) 88 in addition to a green powder from the juice of barley leaves and alfalfa that is equivalent to approximately another 100 g/day of fresh dark greens. So, it is very possible that the range of intakes in the prospective population based studies do not have a wide enough intake on the upper end to detect the true possible impact of a very high intake of fruits and vegetables on cancer risk.

Cruciferous vegetables (broccoli, cauliflower, cabbage, Brussels sprouts) contain sulforophane, which has anti-cancer properties. A case-control study in China found that intake of cruciferous vegetables, measured by urinary secretion of isothiocyanates, was inversely related to the risk of breast cancer; the quartile with the highest intake only had 50% of the risk of the lowest intake group 89. In the Nurses' Health Study a high intake of cruciferous vegetables (5 or more servings/week vs less than two servings/week) was associated with a 33% lower risk of non-Hodgkin's lymphoma 90. In the Health Professionals Follow-up Study bladder cancer was only weakly associated with low intake of fruits and vegetables, but high intake (5 or more servings/week vs 1 or less servings/wk) of cruciferous vegetables was associated with a statistically significant 51% decrease in bladder cancer 91. Also, prostate cancer risk was found to be reduced by cruciferous vegetable consumption in a population-based case-control study carried out in western Washington state. Three or more servings per week, compared to less than one serving of cruciferous vegetables per week resulted in a statistically significant 41% decrease in prostate cancer risk 92. Similar protective effects of cruciferous vegetables were seen in a multi-ethnic case-control study 93. A prospective study in Shanghai, China found that men with detectable amounts of isothiocyanates in their urine (metabolic products that come from cruciferous vegetables) had a 35% decreased risk of lung cancer. Among men that had one or two genetic polymorphisms that caused them to eliminate these isothiocyanates slower there was a 64% or 72% decreased risk of lung cancer, respectively 94.

Broccoli sprouts have a very high concentration of sulforophane since this compound originates in the seed and is not made in the plant as it grows 9596. One sprout contains all of the sulforophane that is present in a full-grown broccoli plant. So, if sulforophane is especially cancer-protective, it would seem reasonable to include some broccoli sprouts in an anti-cancer diet.

Selenium is a mineral with anti-cancer properties. Many studies in the last several years have shown that selenium is a potent protective nutrient for some forms of cancer. The Arizona Cancer Center posted a selenium fact sheet listing the major functions of selenium in the body 97. These functions are as follows:

1. Selenium is present in the active site of many enzymes, including thioredoxin reductase, which catalyze oxidation-reduction reactions. These reactions may encourage cancerous cells to under apoptosis.

2. Selenium is a component of the antioxidant enzyme glutathione peroxidase.

3. Selenium improved the immune systems' ability to respond to infections.

4. Selenium causes the formation of natural killer cells.

5. P450 enzymes in the liver may be induced by selenium, leading to detoxification of some carcinogenic molecules.

6. Selenium inhibits prostaglandins that cause inflammation.

7. Selenium enhances male fertility by increased sperm motility.

8. Selenium can decrease the rate of tumor growth.

A serendipitous randomized, double-blind, controlled trial of a 200 μg/day selenium supplement in the southeastern region of the USA (where soil selenium levels are low) found that the primary endpoints of skin cancer were not improved by the selenium supplement, but that other cancer incidence rates were decreased by selenium 9899. There was a significant reduction in total cancer incidence (105 vs 137 cases, P = 0.03), prostate cancer (22 vs 42 cases, P = 0.005), a marginally significant reduction in colorectal cancer incidence (9 vs 19 cases, P = 0.057), and a reduction in cancer mortality, all cancer sites (40 vs 66 deaths, P = 0.008) (selenium versus control group cases reported, respectively) 98. The selenium supplement was most effective in ex-smokers and for those who began the study with the lowest levels of serum selenium. Several prospective studies have also examined the role of selenium in cancer prevention, particularly for prostate cancer, summarized in Table 2.

Overall, it appears that poor selenium levels, especially for men, are a cancer risk. If a person has low selenium levels and other antioxidant defenses are also low the cancer risk is increased even further. Women do not appear to be as sensitive to selenium, as breast cancer has not been found to be influenced by selenium status in several studies 100101102103104, although both men and women were found to be protected by higher levels of selenium from colon cancer 100 and lung cancer 105106. Good vegetarian sources of selenium are whole grains and legumes grown in selenium-rich soil in the western United States, brazil nuts (by far the most dense source of selenium), nutritional yeast, brewers yeast, and sunflower seeds.

All green plants also contain chlorophyll, the light-collecting molecule. Chlorophyll and its derivatives are very effective at binding polycyclic aromatic hydrocarbons (carcinogens largely from incomplete combustion of fuels), heterocyclic amines (generated when grilling foods), aflatoxin (a toxin from molds in foods which causes liver cancer), and other hydrophobic molecules. The chlorophyll-carcinogen complex is much harder for the body to absorb, so most of it is swept out with the feces. The chemoprotective effect of chlorophyll and its derivatives has been tested in laboratory cell cultures and animals 107108. There is so much compelling evidence for anti-carcinogenic effects of chlorophyll that a prospective randomized controlled trial is being conducted in Qidong, China to see if chlorophyllin can reduce the amount of liver cancer cases, which arise from aflatoxin exposure in their foods (corn, peanuts, soy sauce, and fermented soy beans). A 55% reduction in aflatoxin-DNA adducts were found in the group that took 100 mg of chlorophyllin three times a day 109. It was supposed that the chlorophyllin bound up aflatoxins, but there were chlorophyllin derivatives also detected in the sera (which had a green tint to it) of the volunteers who took the supplement, indicating a possible role in the body besides binding carcinogens in the gut 110.

What is the result when all of these things are put together? What if all of these factors reviewed here were taken into account and put into practice? This anticancer diet would have:

• adequate, but not excessive calories,

• 10 or more servings of vegetables a day, including cruciferous and allium vegetables; vegetable juice could meet part of this goal,

• 4 or more servings of fruits a day,

• high in fiber,

• no refined sugar,

• no refined flour,

• low in total fat, but containing necessary essential fatty acids,

• no red meat,

• a balanced ratio of omega 3 and omega 6 fats and would include DHA,

• flax seed as a source of phytoestrogens,

• supplemented with ~200 μg/day selenium,

• supplemented with 1,000 μg/day methylcobalamin (B-12),

• very rich in folic acid (from dark green vegetables),

• adequate sunshine to get vitamin D, or use 1,000 IU/day supplement,

• very rich in antioxidants and phytochemicals from fruits and vegetables, including α-carotene, β-carotene, β-cryptoxanthin, vitamin C (from foods), vitamin E (from foods),

• very rich in chlorophyll,

• supplemented with beneficial probiotics,

• supplemented with oral enzymes

As reviewed above, reductions of 60 percent in breast cancer rates have already been seen in human diet studies, and a 71 percent reduction in colon cancer for men without the known modifiable risk factors. These reductions are without taking into account many of the other factors considered in this review, such as markedly increased fruit and vegetable intake, balanced omega 3 and 6 fats, vitamin D, reduced sugar intake, probiotics, and enzymes – factors which all are likely to have an impact on cancer. Certainly cancer prevention would be possible, and cancer reversal in some cases is quite likely.

Michael Donaldson is a research scientist at the Hallelujah Acres Foundation, a foundation for investigations pertaining to the Hallelujah Diet. Funding for this review was provided by the Hallelujah Acres Foundation.