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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.

Vitamin E

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.

Selenium

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.

Mixed Antioxidants

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

Beta-carotene

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

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.

Tomatoes (Lycopene)

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.

Vitamin C

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.

Green Tea

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.

Soy

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

For more information, including dosage and safety issues, see the full Soy article.

Folate

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. Only large double-blind, placebo-controlled studies can actually prove a treatment effective, and the only such study performed on folate for cancer prevention found folate ineffective for preventing early colon cancer. ²⁹¹ In fact, this 5 year study of over 1,000 people hinted that folate might increase colon cancer risk. (For an explanation of why observational studies are unreliable, see Why Does This Database Rely On Double-Blind Studies? )

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

One large observational study suggests that higher intake of boron may reduce risk of prostate cancer. ²⁰⁴

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 dindolylmethane (DIM).

One study provides preliminary supporting evidence for the notion that fish oil reduces the risk of prostate cancer; ²²² however, there is no reliable evidence that fish oil has a general cancer-preventive effect. ²⁷⁶

Weak evidence hints that N-acetylcysteine (NAC) treatment may help to prevent colon cancer. ²²³

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.

Vitamin K has shown a slight bit of promise for helping to prevent liver cancer in people with chronic viral hepatitis. ²⁵⁹

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}

Higher level of exercise might potentially help reduce the risk of various forms of cancer, especially colon cancer. ²⁸²

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Last reviewed April 2008 by EBSCO CAM Review Board

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