Cancer Prevention (Reducing the Risk)
• Folate, Garlic, Green Tea, Isoflavones, Selenium, Soy, Tomatoes (Lycopene), Vitamin C, Vitamin E
• Active Hexose Correlated Compound (AHCC), Betulin, Black Tea, Blue-green Algae, Boron, Bromelain, Calcium, Cartilage, Catechins (From Green Tea) , Citrus Bioflavonoids, Conjugated Linoleic Acid, Cordyceps, Coriolus versicolor, Diindolylmethane (DIM), Ellagic Acid, Fiber, Fish Oil, Flaxseed (Lignans), Flavonoid, Genistein, Ginseng, Glycine, Grapes (Resveratrol), Grass Pollen, Indole-3-Carbinol (I3C), Inositol Hexaphosphate (Phytic Acid, IP6), Isoflavones, Kelp, Licorice, Ligustrum, Melatonin, Methyl Sulfonyl Methane (MSM), Milk Thistle, N-Acetylcysteine (NAC), Nettle, Oligomeric Proanthocyanidins (OPCs), Papaw Tree Bark, Probiotics, Quercetin, Rosemary, Schisandra, Shiitake, Sulforaphane, Turmeric, Vitamin D
Cancer is the second major cause of death (next to heart disease) in the United States. It claims the lives of more than half a million Americans each year out of the nearly 1.4 million who get the disease. The probability of getting cancer increases with age. Two-thirds of all cases are in people older than 65. 1
Cancer is believed to begin with a mutation in a single cell. However, a cell doesn't become cancerous overnight. Several mutations in a row are necessary to create all the characteristic features of cancer. Ordinarily, cells have a self-destruct mechanism that causes them to die when their DNA is damaged. However, in developing cancer cells, something interferes with the self-destruct sequence. It may be that the cancer-causing mutations themselves turn off the countdown.
The DNA alterations that create a cancer cell give it a certain independence from the ordinary rules of cell behavior. Normal cells are highly influenced by nearby cells, with the result that they "get along" well with their neighbors. For example, the growth of a healthy cell is ruled by special growth factors given off by surrounding tissues. However, cancer cells either grow without such growth factors or simply make their own. Many types of cancer cells can also trigger the growth of new blood vessels to feed them.
The rate of cancerous mutations is increased by exposure to carcinogenic substances. Cigarette smoke is a powerful carcinogen. Many carcinogens exist in the diet as well, even in fruits and vegetables.
Principal Proposed Natural Treatments
Before we can get into detailed discussion of natural products proposed to help prevent cancer, we must first discuss some fundamental issues regarding the nature of medical evidence.
It is rather difficult to prove that taking a certain supplement will reduce the chance of developing cancer. One really needs enormous long-term, double-blind, placebo-controlled studies in which some people are given the supplement while others are given placebo. However, relatively few studies of this type have been performed.
For most supplements, the evidence that they help prevent cancer comes from observational studies, which are much less reliable. Observational studies have found that people who happen to take in high levels of certain vitamins in their diets develop a lower incidence of specific cancers. However, in such studies it is very difficult to rule out other factors that may play a role. For example, individuals who take vitamins may also exercise more, or take better care of themselves in other ways. Such confounding factors make the results of observational studies less reliable.
Although this may sound like a theoretical issue, it has very practical consequences. For example, based primarily on observational studies, hormone replacement therapy was promoted as a heart-protective treatment for post-menopausal women. However, when placebo-controlled studies were performed, hormone replacement therapy proved to increase the risk of heart disease.
It is now thought that apparent benefits of hormone replacement therapy were due to the fact that woman who used it belonged to a higher socioeconomic class than those who did not use it. (For a variety of reasons, some of which are obscure, higher income is associated with improved health.)
Only a few supplements have any evidence from double-blind trials to support their potential usefulness for cancer prevention, and even that evidence is weak. For all other supplements, supporting evidence is limited to observational studies, as well as preliminary evidence from animal and test tube studies.
The results of observational trials have been mixed, but on balance, they suggest that high intake of vitamin E is associated with reduced risk of many forms of cancer, including stomach, mouth, colon, throat, laryngeal, lung, liver, and prostate cancer. 11,12,14-22,24,46,101
However, as noted above, the results of observational studies are unreliable as guidelines to treatment. The results of double-blind, placebo-controlled studies are far more persuasive in drawing conclusions about cause and effect. Unfortunately, on balance, these studies failed to find vitamin E helpful for the prevention of cancer. 9,13,51-53,263-265,280,301
The one positive note came in a double-blind study of 29,133 smokers. Those who were given 50 mg of synthetic vitamin E (dl-alpha-tocopherol) daily for 5 to 8 years showed a 32% reduction in the incidence of prostate cancer and a 41% drop in prostate cancer deaths. 9 Surprisingly, results were seen soon after the beginning of supplementation. This was unexpected because prostate cancer grows very slowly. A cancer that shows up in the prostate today actually started to develop many years ago. The fact that vitamin E almost immediately lowered the incidence of prostate cancer suggests that it may somehow block one of the last steps in the development of detectable prostate cancer.
Nonetheless, the negative results regarding most other types of cancer have made scientists hesitant to place too much hope in these findings. Some researchers believe that better results will be seen with a form of vitamin E called gamma-tocopherol rather than the alpha-tocopherol used in the trials mentioned above. 290 Others suggest that vitamin E might be more helpful for cancer prevention in low-risk people. Further research is currently underway to help settle these questions.
For more information, including dosage and safety issues, see the full Vitamin E article.
It has long been known that severe selenium deficiency increases the risk of cancer. 29 One double-blind study found some evidence that selenium supplements might help prevent cancer even in the absence of severe deficiency. 30 The study actually designed to detect selenium's effects on skin cancer. It followed 1,312 individuals, half of whom were given 200 mcg of selenium daily. People participating in the study were not deficient in selenium. The participants were treated for an average of 2.8 years and were followed for about 6 years. Although no significant effect on skin cancer was found, the researchers were startled when the results showed that people taking selenium had a 50% reduction in overall cancer deaths and significant decreases in cancer of the lung (40%), colon (50%), and prostate (66%). The findings were so remarkable that the researchers felt obliged to break the blind and allow all the participants to take selenium.
Subsequent re-evaluation of the results, including additional data from follow-up, indicated that lung cancer and colon cancer benefits were seen only in participants with somewhat low levels of selenium in the blood to begin with. 54,266 (At the time of this writing, researchers had not announced whether the same was true regarding prostate cancer prevention.)
While this evidence is promising, it has one major flaw: The laws of statistics tell us that when researchers start to deviate from the question their research was designed to answer, the results may not be trustworthy. As an illustration of this, yet another after-the-fact statistical analysis of the data hints selenium supplements might actually increase risk of certain forms of skin cancer. 250 This, however, may not be a real concern either, as all such statistical manipulation is suspect.
One study published in 2007 evaluated whether selenium supplements could help prevent skin cancer in transplant patients. 285 People who have undergone organ transplants are at particularly high risk of skin cancer linked to the human papilloma virus (HPV). In this double-blind study, 184 organ transplant recipients were given either placebo or selenium at a dose of 200 mg daily. The results over two years failed to show benefit: both the placebo and the selenium group developed precancerous and cancerous lesions at the same rate. The bottom line: Further research will be necessary before we know whether selenium supplements actually help prevent cancer.
For more information, including dosage and safety issues, see the full Selenium article.
A large double-blind, placebo-controlled study evaluated the potential overall cancer preventive benefits of a low-dose combination antioxidant supplement providing 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta-carotene, 100 mcg of selenium, and 20 mg of zinc taken daily for about 7.5 years. 251 The results as a whole failed to show benefit. However, analysis by sex showed a significant reduction in cancer incidence in men but not in women. It is not clear whether these results are meaningful. The researchers involved in this study concluded the following: Low dose antioxidant supplementation may be helpful in healthy people, without cancer risk, who are deficient in antioxidant nutrition. High doses of antioxidants may be harmful for people who are at higher risk for cancer and may already be in the initial phases of cancer development. Finally, antioxidants in high or low doses are probably not helpful in healthy people with good nutrition. 279
Another large study failed to find mixed antioxidants helpful for preventing stomach cancer in particular. 284 And, in a meta-analysis (detailed mathematical review) of 20 high-quality, randomized trials (involving a total of 211,818 participants), researchers concluded that neither beta-carotene, vitamin A, vitamin C, vitamin E, or selenium effectively lowered the risk of gastrointestinal cancers. If anything, they may have slightly increased the risk of death from these cancers.308
The story of beta-carotene and cancer is full of contradictions. It starts in the early 1980s, when the cumulative results of many studies suggested that people who eat a lot of fruits and vegetables are significantly less likely to get cancer. 55,56 A close look at the data pointed to carotenes as the active ingredients in fruits and vegetables. It appeared that a high intake of dietary carotene might significantly reduce the risk of cancers of the lung, 57 bladder, 58 breast, 59 esophagus, 60 and stomach. 11
However, as noted above, observational studies cannot prove cause and effect. When researchers gave beta-carotene to study participants, the results have been impressively negative.
Most studies enrolled people in high-risk groups, such as smokers, because it is easier to see results when you look at people who are more likely to develop cancer to begin with.
The anticancer bubble burst for beta-carotene in 1994 with the results of the Alpha-Tocopherol, Beta-carotene (ATBC) study. 13 These results showed that beta-carotene supplements did not prevent lung cancer, but actually increased the risk of getting it by 18%. This trial followed 29,133 male smokers in Finland who took supplements of about 50 IU of vitamin E (alpha-tocopherol), 20 mg of beta-carotene (more than 10 times the amount necessary to provide the daily requirement of vitamin A), both, or placebo daily for 5 to 8 years. (In contrast, vitamin E was found to reduce the risk of cancer, especially prostate cancer.)
In January 1996, researchers monitoring the Beta-carotene and Retinol Efficacy Trial (CARET) confirmed the prior bad news with more of their own: The beta-carotene group had 46% more cases of lung cancer deaths. 64 This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial 21 months before it was planned to end.
At about the same time, the 12-year Physicians' Health Study of 22,000 male physicians was finding that 50 mg of beta-carotene (about 25 times the amount necessary to provide the daily requirement of vitamin A) taken every other day had no effect—good or bad—on the risk of cancer or heart disease. In this study, 11% of the participants were smokers and 39% were ex-smokers. 65,66
Similarly, another study of beta-carotene supplements failed to find any effect on the risk of cancer in women. 67 And, in a final indictment of beta-carotene’s safety and effectiveness, researchers, who combined the results of 12 recent placebo-controlled trials investigating the association between antioxidant supplementation and cancer, found that beta-carotene use was associated with an increased incidence of cancer among smokers.304 But the story doesn’t end there. In yet another careful analysis of 4 randomized trials involving 109,394 smoker and former-smokers, researchers found that current smokers who consumed between 20-30 mg of beta-carotene were at significantly greater risk of developing lung cancer. There was no such risk among former smokers.305
What is the explanation for these discrepancies? One possibility is that beta-carotene alone is not effective. Fruits and vegetables contain many carotenoids (carotene-like substances) that may be more important for preventing cancer than beta-carotene. One researcher has suggested that taking beta-carotene supplements actually depletes the body of other beneficial carotenoids. 69
It is also possible that intake of carotenes as such are unrelated to cancer and that some unrelated factor common to individuals with a high carotene diet is the cause of the benefits seen in observational trials.
For more information, including dosage and safety issues, see the full Beta-carotene article.
Lycopene, a carotenoid like beta-carotene, is found in high levels in tomatoes and pink grapefruit. Lycopene appears to exhibit about twice the antioxidant activity of beta-carotene and may be more helpful for preventing cancer.
In one observational study, elderly Americans consuming a diet high in tomatoes showed a 50% reduced incidence of cancer. 70 Men and women who ate at least seven servings of tomatoes weekly developed less stomach and colorectal cancers compared to those who ate only two servings weekly.
In another study, 47,894 men were followed for 4 years in an observational study looking for influences on prostate cancer. 71 Their diets were evaluated on the basis of how often they ate fruits, vegetables, and foods containing fruits and vegetables. High levels of tomatoes, tomato sauce, and pizza in the diet were strongly connected to reduced incidence of prostate cancer. After an evaluation of known nutritional factors in these foods as compared to other foods, lycopene appeared to be the common denominator. Additional impetus has been given to this idea by the discovery of lycopene in reasonably high levels in the human prostate, 72 evidence from test tube studies that lycopene might slow DNA synthesis in prostate cells, 281 and evidence that men with higher lycopene levels in the blood have a lower risk of prostate cancer. 73
Similarly weak evidence suggests that foods containing lycopene might help prevent other forms of cancer as well, including lung, colon, and breast cancer. 68,74,112
A few poorly designed intervention trials have also been performed, and these suggest that lycopene or a standardized tomato extract containing lycopene might be helpful for the prevention or treatment of prostate or breast cancer. 267-269
For more information, including dosage and safety issues, see the full Lycopene article.
Several observational studies have found a strong association between high dietary vitamin C intake and a reduced incidence of stomach cancer. 76,78 It has been proposed that vitamin C may prevent the formation of carcinogenic substances known as N-nitroso compounds in the stomach.
Observational studies have also linked higher vitamin C in the diet with reduced risk of cancers of the colon, esophagus, larynx, bladder, cervix, rectum, breast, and perhaps lung. 12,76,79,82-84 However, dietary vitamin C intake does not appear to be associated with reduced rate of prostate cancer. 85
One study found that vitamin C supplementation at 500 mg or more daily was associated with a lower incidence of bladder cancer. 86 However, another study found no association. 87 Similarly, in another observational study, 500 mg or more of vitamin C daily over a period of 6 years was not associated with reduced incidence of breast cancer. 89 Another study found similar results. 90
For more information, including dosage and safety issues, see the full Vitamin C article.
Both green tea and black tea come from the plant Camellia sinensis , which has been cultivated in China for centuries. The key difference between the two is in preparation. For black tea, the leaves are allowed to oxidize, a process believed to lessen the potency of the presumed active ingredients in green tea, catechin polyphenols. Green tea is made by lightly steaming the freshly cut leaf, a process that prevents oxidation and possibly preserves more of the therapeutic effects.
Laboratory and animal studies suggest that tea consumption protects against cancers of the stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon. 91,92 A 1994 study of skin cancer in mice found that both black and green teas, even decaffeinated versions, inhibited skin cancer in mice exposed to ultraviolet light and other carcinogens. 93,94 After 31 weeks, mice given the teas brewed at the same concentration humans drink had 72% to 93% fewer skin tumors than mice given only water.
However, results from observational studies in humans have not been so clear-cut—some have found evidence of a protective effect, and others have not. 95
One study followed 8,552 Japanese adults for 9 years. 96 Women who drank more than 10 cups of green tea daily had a delay in the onset of cancer and also a 43% lower total rate of cancer occurrence. Males had a 32% lower cancer incidence, but this finding was not statistically significant.
A study in Shanghai, China, found that those who drank green tea had significantly less risk of developing cancers of the rectum and pancreas than those who did not. No significant association with colon cancer incidence was found. 97 A total of 3,818 residents aged 30 to 74 were included in the population study. For men, those who drank the most tea had a 28% lower incidence of rectal cancer and a 37% lower incidence of pancreatic cancer compared to those who did not drink tea regularly. For women, the respective differences in cancer frequency were even greater: 43% and 47%.
Another study in Shanghai found similar associations for stomach cancer. Green tea drinkers were 29% less likely to get stomach cancer than nondrinkers, with those drinking the most tea having the least risk. 98 Interestingly, the risk of stomach cancer did not depend on the person's age at which he or she started drinking green tea. Researchers suggested that green tea may disrupt the cancer process at both the intermediate and the late stage.
However, in an observational study of 26,311 Japanese individuals, no reduction in stomach cancer rates were seen. 99 Lack of benefit was also seen in a study conducted in Hawaii. 100 In any case, observational studies are intrinsically unreliable.
Green tea may exert an estrogen-blocking effect that is helpful in preventing breast and uterine cancer, 103 and another study suggests that it might prevent the development of tumors by blocking the growth of new blood vessels. 104
The main catechin polyphenol found in green tea is epigallocatechin gallate (EGCG). Preliminary experimental studies suggest that EGCG may help prevent skin cancer if it is applied directly to the skin. 102
For more information, including dosage and safety issues, see the full Green Tea article.
In many animal studies, soybeans, soy protein, or other soy extracts decreased cancer risk, and observational studies in people have found suggestive associations between higher soy consumption and lower incidence of hormone-related cancers such as prostate, breast, and uterine cancer. 105-111
Soybeans provide estrogen-like compounds known as isoflavones , especially genistein and daidzein. These substances bind to the same sites in the body as estrogen, occupying these sites and keeping natural estrogen away. Estrogen stimulates certain forms of cancer, but soy isoflavones exert a milder estrogen-like effect that may not stimulate cancer as much as natural estrogen. This could help protect against cancer. Soy may additionally reduce levels of the body’s own estrogen, which would also have a protective effect. 2,3,15,22,44,82
However, not all evidence on soy and cancer is positive. Because the isoflavones work somewhat like estrogen, there are theoretical concerns that they may not be safe for women who have already had breast cancer. Studies in animals have found suggestive evidence that under certain circumstances soy isoflavones might stimulate breast cancer cells. 60,61,63 Furthermore, evidence from two preliminary studies in humans found changes suggesting that soy might slightly increase breast cancer risk. 3,65 Other studies in women have found reassuring results; nonetheless, prudence suggests that women who have had breast cancer, or are at high risk for it, should consult a physician before taking any isoflavone product. 75
Men have very low levels of circulating estrogen, so the net effect of increased soy consumption might be to increase estrogen-like activity in the body. Since real estrogen is used as a treatment to suppress prostate cancer, it has been hypothesized that the mild estrogen-like activity of isoflavones has a similar effect. There are also indications that isoflavones might decrease testosterone levels, and alter ratios of certain forms of estrogen, both of which would be expected to provide benefit. 297,298 Thus, there are several possible ways in which isoflavones might be useful for preventing or treating prostate cancer. Whether or not they actually help has been tested in a few preliminary trials.
For example, in one double-blind study, men with early prostate cancer were given either isoflavones or placebo, and their PSA levels were monitored. 252 (PSA is a marker for prostate cancer, with higher values generally showing an increased number of cancer cells.) The results did show that use of isoflavones (60 mg daily) slightly reduces PSA levels. Whether this meant that soy actually slowed the progression of the cancer or simply lowered PSA directly is not clear from this study alone. However, another study of apparently healthy men (not known to have prostate cancer) found that soy isoflavones at a dose of 83 mg per day did not alter PSA levels. 299 Taken together, these two studies provide some direct evidence that soy isoflavones may be helpful for treating or preventing prostate cancer, but the case, nonetheless, remains highly preliminary.
A special highly concentrated extract of soy, Bowman-Birk Inhibitor (BBI), has also shown promise for helping to prevent various types of cancer. 286-289
There exists weak evidence that besides the isoflavone found in soy, flavonoids (found, for example, in beans, onions, apples, and tea) may reduce the recurrence of colorectal polyps, common precancerous lesions found in the colon and rectum.307
For more information, including dosage and safety issues, see the full Soy article.
Observational studies have suggested that folate deficiency may predispose individuals toward developing cancer of the cervix, 120 colon, 121,122 lung, 123 breast, 124 pancreas, 125 and mouth. 123 Other observational studies have suggested that folate supplements may help prevent colon cancer, especially when it is taken for many years, or by people with ulcerative colitis.20,127,129,253,290 However, observational studies are notoriously unreliable; large double-blind, placebo-controlled studies are needed to prove a treatment effective. One such study performed on folate for cancer prevention among 1,000 people over a 5-year period found folate ineffective for preventing early colon cancer.140 However, a much smaller study involving 94 individuals with colon polyps (a precancerous condition) found that folate may reduce the risk of recurrent polyps over a 3-year period.309
For more information, including dosage and safety issues, see the full Folate article.
Other Proposed Natural Treatments
Some, but not all, observational and intervention studies have found evidence that calcium supplementation may reduce the risk of colon cancer. 130-139,270-272,302 Risk reduction might continue for years after calcium supplements are stopped. 283 In men, however, calcium supplements might increase risk of prostate cancer. 273-274 For menopausal women, calcium supplementation, especially when taken along with vitamin D, appears to reduce overall cancer incidence. 292
Some studies have connected higher vitamin D levels with a lower incidence of cancer of the breast, colon, pancreas, and prostate, as well as melanoma, but overall research has yielded mixed results. 130,140-142,144-159,275
Increasing dietary fiber has long been thought to help reduce the incidence of colon polyps. 160-163 However, several recent studies have found either little evidence of benefit or none at all. 41,165-170 For example, one very large study enrolled almost 2,000 people with a history of colon polyps and compared the ordinary American diet against a diet very high in fiber, fruits and vegetables, as well as low in saturated fat. 294 Over the four years of the study, plus an additional four years of follow-up, this presumably “healthier” diet failed to reduce polyp recurrence.
Substances known as lignans are found in several foods and may produce anticancer benefits. They are converted in the digestive tract to estrogen-like substances known as enterolactone and enterodiol. 106,172 Like soy isoflavones (see the previous discussion under the heading Soy ), these substances prevent estrogen from attaching to cells and may thereby block its cancer-promoting effects. Lignans are found most abundantly in flaxseed , a high-fiber grain that has been cultivated since ancient Egyptian times. Both flaxseed and flaxseed oil have been recommended for prevention or treatment of cancer, but the supporting evidence is still extremely preliminary. 106,173-176,178-181 Contrary to some reports, flaxseed oil contains no lignans. 173 Instead, it contains the alpha-linolenic acid, which is also hypothesized to have cancer-preventive effects.
Evidence from observational studies suggests that garlic taken in the diet as food may help prevent cancer, particularly cancer of the colon and stomach. 36-43 In one of the best of these studies, the Iowa Women's Study, women who ate significant amounts of garlic were found to be about 30% less likely to develop colon cancer. 41,44 Similar results were seen in other observational studies performed in China, Italy, and the United States. 37,45,295 In addition, one preliminary intervention trial also found a bit of evidence that aged garlic may reduce risk of colon cancer. 296
Resveratrol is a phytochemical found in at least 72 different plants, including mulberries and peanuts. Grapes and red wine are particularly rich in resveratrol. This substance has shown anticancer properties in test tube studies. 186,187
Provocative evidence suggests that a substance called sulforaphane , found in broccoli and related vegetables, may possess anticancer properties. 205,207 Recently, broccoli sprouts have been touted for cancer prevention on the basis of their high content of sulforaphane. However, this recommendation is still highly speculative. Another constituent of broccoli-family vegetables, indole-3-carbinol , has also shown promise as a cancer-preventative agent; 208-212 however, there is some evidence that this substance might actually increase the risk of cancer in certain circumstances. 213,214 Much the same is true of the related substance diindolylmethane (DIM).
In one large randomized controlled trial, diets rich in fish and omega-3 fatty acids from fish were associated with a significant reduction in the risk of developing colorectal cancer among men over a 22-year period.306 Another study provides preliminary supporting evidence for the notion that fish oil reduces the risk of prostate cancer.222 However, on balance, there is still relatively little evidence that the consumption of fish oil reduces the risk of cancer.276
Several studies have experimented with using very high doses of vitamin A to prevent skin cancer, doses considerably above levels ordinarily considered safe. Some have found possible benefits regarding preventing some forms of skin cancer, while others have not. 256-258 This approach should not be tried except under physician supervision.
Innumerable other herbs and supplements have shown minimal promise in test tube and animal studies, including but not limited to active hexose correlated compound (AHCC), cordyceps , Coriolus versicolor , ligustrum , quercetin , citrus bioflavonoids , conjugated linoleic acid , Morina citrifolia ( noni ), turmeric , rosemary , betulin (from white birch tree), bromelain , ellagic acid (from grapes, raspberries, strawberries, apples, walnuts, and pecans), ginseng , glycine , grass pollen , inositol hexaphosphate (phytic acid, IP6), kelp , licorice , melatonin , MSM , milk thistle , nettle , OPCs (oligomeric proanthocyanidins) , papaw tree bark, probiotics or "friendly" bacteria, royal jelly , shiitake , schisandra , and blue-green algae . 80,105,184,187,216-218,219,220,221,224-249,255,293
While it is commonly stated as a fact that high consumption of fruits and vegetables reduces cancer risk, the evidence is limited to inherently unreliable observational studies, and even among these the results are inconsistent. 126,128,143,164,171,177,182,183,260 As noted earlier , a large study failed to find that a diet high in fruits and vegetables reduced risk of colon polyps. 294 Similarly, meat consumption, widely stated to increase colon cancer risk, might or might not do so—the evidence is not compelling. 81,261 Current data does not suggest that diets high in sugar or other simple carbohydrates increase colon cancer risk, 262 or that reducing fat in the diet reduces colon, uterine, or breast cancer risk. 277-278,300,303
9. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.
11. Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol. 1995;142:955-959.
13. Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(suppl):1427S-1430S.
18. Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64:190-196.
21. Malila N, Virtamo J, Virtanen M, et al. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiol Biomarkers Prev. 1999;8:489-493.
22. Lu LJW, Anderson KE, Grady JJ, et al. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev. 1996;5:63-70.
30. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin: a randomized controlled trial. Nutritional Prevention of Cancer Study. JAMA. 1996;276:1957-1963.
46. Michaud DS, Pietinen P, Taylor PR, et al. Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer. 2002;87:960-965.
51. Malila N, Taylor PR, Virtanen MJ, et al. Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland). Cancer Causes Control. 2002;13:617-623.
52. Virtamo J, Edwards BK, Virtanen M, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tracct cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control. 2000;11:933-939.
53. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23-33.
54. Reid ME, Duffield-Lillico AJ, Garland L, et al. Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev. 2002;11:1285-1291.
60. Allred CD, Allred KF, Ju YH, et al. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 2001;61:5045-5050.
61. Ju YH, Allred CD, Allred KF, et al. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001;131:2957-2962.
66. Frieling UM, Schaumberg DA, Kupper TS, et al. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the Physicians' Health Study. Arch Dermatol. 2000;136:179-184.
69. White WS, Stacewicz-Sapuntzakis M, Erdman JW Jr, et al. Pharmacokinetics of beta-carotene and canthaxanthin after ingestion of individual and combined doses by human subjects. J Am Coll Nutr. 1994;13:665-671.
75. Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.
79. Shibata A, Paganini-Hill A, Ross RK, et al. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer. 1992;66:673-679.
84. Khaw KT, Bingham S, Welch A, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. Lancet. 2001;357:657-663.
93. Wang ZY, Huang MT, Lou YR, et al. Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[ a ] anthracene-initiated SKH-1 mice. Cancer Res. 1994;54:3428-3435.
100. Galanis DJ, Kolonel LN, Lee J, et al. Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study. Int J Epidemiol. 1998;27:173-180.
125. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol. 2001;153:680-687.
135. Bostick RM, Fosdick L, Wood JR, et al. Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial. J Natl Cancer Inst. 1995;87:1307-1315.
137. Holt PR, Atillasoy EO, Gilman J, et al. Modulation of abnormal colonic epithelial cell proliferation and differentiation by low-fat dairy foods: a randomized controlled trial. JAMA. 1998;280:1074-1079.
143. Norat T, Van Bakel M, Riboli E. Fruit and vegetable consumption and risk of cancer of the digestive tract: meta-analysis of published case-control and cohort studies. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.
152. Hofer H, Ho GM, Peterlik M, et al. Biological effects of 1alpha-hydroxy- and 1beta-(hydroxymethyl)-vitamin D compounds relevant for potential colorectal cancer therapy. J Pharmacol Exp Ther. 1999;291:450-455.
153. Tong WM, Kallay E, Hofer H, et al. Growth regulation of human colon cancer cells by epidermal growth factor and 1,25-dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression. Eur J Cancer. 1998;34:2119-2125.
158. Danielsson C, Torma H, Vahlquist A, et al. Positive and negative interaction of 1,25-dihydroxyvitamin D3 and the retinoid CD437 in the induction of human melanoma cell apoptosis. Int J Cancer. 1999;81:467-470.
161. Howe GR, Benito E, Castelleto R, et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst. 1992;84:1887-1896.
167. MacLennan R, Macrae F, Bain C, et al. Randomized trial of intake of fat, fiber, and beta carotene to prevent colorectal adenomas. The Australian Polyp Prevention Project. J Natl Cancer Inst. 1995;87:1760-1766.
168. McKeown-Eyssen GE, Bright-See E, Bruce WR, et al. A randomized trial of low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group. J Clin Epidemiol. 1994;47:525-536.
170. Alberts DS, Martinez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med. 2000;342:1156-1162.
172. Adlercreutz H, Fotsis T, Heikkinen R, et al. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet. 1982;2:1295-1299.
175. Bougnoux P, Koscielny S, Chajes V, et al. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. Br J Cancer. 1994;70:330-334.
182. Bidoli E, La Vecchia C, Talamini R, et al. Micronutrients and ovarian cancer: a case-controlled study in Italy. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.
193. Oikawa T, Ashino-Fuse H, Shimamura M, et al. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett. 1990;51:181-186.
194. McGuire TR, Kazakoff PW, Hoie EB, et al. Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy. 1996;16:237-244.
197. Jamali M-A, Riviere M, Falardeau P, et al. Effect of AE-941 (Neovastat), an angiogenesis inhibitor, in the Lewis lung carcinoma metastatic model, efficacy, toxicity prevention and survival. Clin Invest Med. 1998;(suppl):S16.
199. Riviere M, Alaoui-Jamali M, Falardeau P, et al. Neovastat: an inhibitor of angiogenesis with anti-cancer activity. Presented at: Proceedings of the American Association for Cancer Research Annual Meeting 39; March 28-April 1, 1998; New Orleans, LA.
200. Blasecki J, Alaoui-Jamali M, Wang T, et al. Oral administration of Neovastat inhibits tumor progression in animal models of progressive tumor growth and metastasis. Int J Oncol. 1997;11(suppl):934.
201. Dupont E, Alaoui-Jamali M, Wang T, et al. Angiostatic and antitumoral activity of AE-941 (Neovastat), a molecular fraction derived from shark cartilage. Presented at: Proceedings of the American Association for Cancer Research Annual Meeting 38; April 12-16, 1997; San Diego, CA.
210. Chen I, Safe S, Bjeldanes L. Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. Biochem Pharmacol. 1996;51:1069-1076.
212. Background information. Indole-3-carbinol (I3C). National Institute of Environmental Health Sciences website. Available at: http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Indolecarbinoll . Accessed September 19, 2000.
215. Arts IC, Jacobs DR Jr, Folsom AR. Dietary catechins and cancer incidence: the Iowa Women's Health Study. Presented at: European Conference on Nutrition and Cancer; June 21-24, 2001; Lyon, France.
226. Tham DT, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.
230. Mishima T, Murata J, Toyoshima M, et al . Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.Clin Exp Metastasis. 1998;16:541-550.
253. Diculescu M, Ciocirlan M, Ciocirlan M, et al. Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients with ulcerative colitis: the old and new evidence. Rom J Gastroenterol. 2004;12:283-286.
257. Levine N, Moon TE, Cartmel B, et al. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6:957-961.
258. Moon TE, Levine N, Cartmel B, et al. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997;6:949-956.
266. Reid ME, Duffield-Lillico AJ, Sunga A, et al. Selenium supplementation and colorectal adenomas: An analysis of the nutritional prevention of cancer trial. Int J Cancer. 2005 Oct 10. [Epub ahead of print]
277. Beresford SA, Johnson KC, Ritenbaugh C, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:643-654.
278. Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295:629-642.
281. Barber NJ, Zhang X, Zhu G, et al. Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study. Prostate Cancer Prostatic Dis. 2006 Sep 19. [Epub ahead of print]
284. Plummer M, Vivas J, Lopez G, et al. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst. 2007;99:137-146.
286. Armstrong WB, Kennedy AR, Wan XS, et al. Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clin Cancer Res. 2000;6:4684-4691.
289. Armstrong WB, Wan XS, Kennedy AR, et al. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope. 2003;113:1687-1702.
290. Wright ME, Weinstein SJ, Lawson KA, et al. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2007;16:1128-1135.
294. Lanza E, Yu B, Murphy G, et al. The polyp prevention trial continued follow-up study: no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization. Cancer Epidemiol Biomarkers Prev. 2007;16:1745-1752.
297. Hamilton-Reeves JM, Rebello SA, Thomas W, et al. Soy protein isolate increases urinary estrogens and the ratio of 2:16 alpha-hydroxyestrone in men at high risk of prostate cancer. J Nutr. 2007;137:2258-2263.
298. Goldin BR, Brauner E, Adlercreutz H, et al. Hormonal response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects. Nutr Cancer. 2005;51:1-6.
299. Adams KF, Chen C, Newton KM, et al. Soy isoflavones do not modulate prostate-specific antigen concentrations in older men in a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2004;13:644-648.
300. Prentice RL, Thomson CA, Caan B, et al. Low-fat dietary pattern and cancer incidence in the women's health initiative dietary modification randomized controlled trial. J Natl Cancer Inst. 2007 Oct 9. [Epub ahead of print]
301. Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008;83:23-34.
304. Bardia A, Tleyjeh IM, Cerhan JR, et al. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008;83:23-34.
305. Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer. 2008 Apr 21.
308. Bjelakovic G, Nikolova D, Simonetti RG, et al. Systematic review and meta-analysis: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements. Aliment Pharmacol Ther. 2008 Jun 30.
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