Cancer Prevention (Reducing the Risk)
En Español (Spanish Version)
Principal Proposed Natural Treatments
Folate ; Garlic ; Green Tea ; Isoflavones ; Selenium ; Soy ; Tomatoes (Lycopene) ; Vitamin C ; Vitamin E
Other Proposed Natural Treatments
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) ; Omega-3 Fatty Acids ;Papaw Tree Bark; Probiotics ; Quercetin ; Rosemary ; Schisandra ; Shiitake ; Sulforaphane ; Turmeric ;Vitamin B; Vitamin D
Probably Not Effective Treatments
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.
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.11,12,14-22,24,46,101,310
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.29One 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 increaserisk 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.251The 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.284And, 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
On the other hand, a review of 22 case-controlled studies with 10,073 women did find evidence that vitamin or antioxidant supplementation may reduce the risk of cervical dysplasia(which can lead to cervical cancer).319 Supplements that may offer this protective benefit include beta-carotene, vitamin C, vitamin E, and vitamin B12. While these results seem more promising, case-controlled studies are less reliable than randomized, controlled studies and sometimes serve to cloud the picture rather clarify it.
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.55,56A 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,57bladder,58breast,59esophagus,60and 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.67And, 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.304But 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.71Their 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,72evidence from test tube studies that lycopene might slow DNA synthesis in prostate cells,281and 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.12,76,79,82-84However, 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.86However, another study found no association.87Similarly, 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.89Another 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.91,92A 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.
Green tea may exert an estrogen-blocking effect that is helpful in preventing breast and uterine cancer,103and another study suggests that it might prevent the development of tumors by blocking the growth of new blood vessels.104A review of 9 studies (none of which were clinical trials) involving over 5,600 cases of breast found weak evidence for reduction in breast cancer recurrence among people who consumed more than 3 cups of green tea every day.317 But, they failed to find reliable evidence for a reduction in the incidence of breast cancer.
However, in an observational study of 26,311 Japanese individuals, researchers saw no reduction in stomach cancer rates.99Lack of benefit was also seen in a study conducted in Hawaii.100And, combining the results of 13 observational studies, researchers found conflicting evidence for green tea’s effect on the risk of stomach cancer.312However, in a small Japanese randomized trial, patients who supplemented their regular diet with an extra 1.5 g of green tea extract per day for 1 year lowered their risk of recurrent colorectal polyps compared to those who took no supplement.313
In a review of multiple studies including 43 observational studies, 4 randomized trials and 1 metanalysis (mathematical summation of the results from several studies), researchers concluded that there was inconsistent evidence supporting green tea’s effectiveness for cancer prevention.311
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 genisteinand 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 alreadyhad breast cancer. Studies in animals have found suggestive evidence that under certain circumstances soy isoflavones might stimulate breast cancer cells.60,61,63Furthermore, evidence from two preliminary studies in humans found changes suggesting that soy might slightly increase breast cancer risk.3,65Other 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 studieshave suggested that folate deficiency may predispose individuals toward developing cancer of the cervix,120colon,121,122lung,123breast,124pancreas,125and 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.20,127,129,253,290However, 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 And, in a large controlled trial involving over 5,400 women, supplements combining folate plus vitamins B 6 and B 12taken for 7 years did not reduce the risk of a cancer compared to a placebo.315However, 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.
Last reviewedJuly 2012by EBSCO CAM Review Board
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.