What are natural treatments for cancer risk reduction?

Principal Proposed Natural Treatments

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 studied 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 difficult to rule out other factors that may play a role. For example, persons 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 (HRT) was promoted as a heart-protective
treatment for postmenopausal women. However, when placebo-controlled studies were
performed, HRT proved to increase the risk of heart disease.

It is now thought that the apparent benefits of HRT arose because women who
used it often 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 and to
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. However, 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. On balance, these studies failed to find
vitamin E helpful for the prevention of cancer.

The one positive note came in a double-blind study of 29,133 smokers. Those who
were given 50 milligrams (mg) of synthetic vitamin E (dl-alpha-tocopherol) daily
for five to eight years showed a 32 percent reduction in the incidence of
prostate
cancer and a 41 percent drop in prostate cancer deaths.
Surprisingly, results were seen soon after the beginning of supplementation. This
was unexpected because prostate cancer develops slowly. A cancer that shows up in
a man’s prostate today actually started to develop many years ago. 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 foregoing trials. Others suggest that vitamin E might be more helpful for cancer prevention in low-risk people.

Selenium. It has long been known that severe selenium deficiency
increases the risk of cancer. One double-blind study found some evidence that
selenium supplements might help prevent cancer even in the absence of severe
deficiency. The study was designed to detect selenium’s effects on
skin
cancer. It followed 1,312 persons, one-half of whom were
given 200 micrograms (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 six 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 percent reduction in overall cancer deaths and
significant decreases in cancer of the lung (40 percent), colon (50 percent), and
prostate (66 percent). The findings were so remarkable that the researchers felt
obliged to break the blind and allow all the participants to take selenium.

Subsequent reevaluation 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. While this evidence is promising, it has one major flaw: The laws of statistics indicate 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 that selenium supplements might actually increase the risk of certain forms of skin cancer. 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. 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 group
and the selenium group developed precancerous and cancerous lesions at the same
rate. Further research will be necessary before it is known whether selenium
supplements actually help prevent cancer.

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. The results as a whole failed to show benefit. However,
analysis by gender 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.

Another large study failed to find mixed antioxidants helpful for preventing
stomach cancer in particular. In a meta-analysis (a detailed mathematical
review) of twenty high-quality randomized trials (involving 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.

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. 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, bladder, breast, esophagus, and
stomach.

However, once again, observational studies cannot prove cause and effect. When researchers gave beta-carotene to study participants, the results have been impressively negative.

Beta-carotene’s reported benefits came under question in 1994 with the results
of the Alpha-Tocopherol, Beta-Carotene study. These results showed that
beta-carotene supplements did not prevent lung cancer
but actually increased the risk of getting it by 18 percent. This trial followed
29,133 male smokers in Finland who took supplements of about 50 international
units (IU) of vitamin E (alpha-tocopherol), 20 mg of beta-carotene (more than ten
times the amount necessary to provide the daily requirement of vitamin A), both,
or placebo daily for five to eight 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 earlier negative news with more of their own: The beta-carotene group had 46 percent more cases of lung cancer deaths. This study involved smokers, former smokers, and workers exposed to asbestos. Alarmed, the National Cancer Institute ended the $42 million CARET trial twenty-one months before it was scheduled to end.

At about the same time, the twelve-year Physicians’ Health Study of 22,000 male physicians was finding that 50 mg of beta-carotene (about twenty-five 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 percent of the participants were smokers and 39 percent were former smokers.

Similarly, another study of beta-carotene supplements failed to find any effect on the risk of cancer in women. In a final indictment of beta-carotene’s safety and effectiveness, researchers, who combined the results of twelve 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. However, the story does not end there. In yet another careful analysis of four randomized trials involving 109,394 smokers and former smokers, researchers found that smokers who consumed between 20 and 30 mg of beta-carotene were at significantly greater risk of developing lung cancer. There was no such risk among former smokers.

One possible explanation for these discrepancies 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 suggested that taking beta-carotene supplements actually depletes the body of other beneficial carotenoids. It is also possible that intake of carotenes as such is unrelated to cancer and that some unrelated factor common to persons with a high carotene diet is the cause of the benefits seen in observational trials.

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 percent reduced incidence of cancer. 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 four years in an observational study looking for influences on prostate cancer. 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 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, evidence from test-tube studies that lycopene might slow DNA synthesis in prostate cells, and evidence that men with higher lycopene levels in the blood have a lower risk of prostate cancer. Similarly weak evidence suggests that foods containing lycopene might help prevent other forms of cancer, including lung, colon, and breast cancer. 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.

Vitamin C. Several observational studies have found a strong
association between high dietary vitamin C intake and a reduced
incidence of stomach cancer. 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. However, dietary vitamin C intake does not appear to be associated with reduced rate of prostate cancer.

One study found that vitamin C supplementation at 500 mg or more daily was associated with a lower incidence of bladder cancer. However, another study found no association. Similarly, in another observational study, 500 mg or more of vitamin C daily for six years was not associated with reduced incidence of breast cancer. Another study found similar results.

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. 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. After thirty-one weeks, mice given the teas brewed at the same concentration humans drink had 72 to 93 percent fewer skin tumors than mice that were 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. One study followed 8,552 Japanese adults for nine years. Women who drank more than ten cups of green tea daily had a delay in the onset of cancer and also a 43 percent lower total rate of cancer occurrence. Men had a 32 percent 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. A total of 3,818 residents age thirty to seventy-four years were included
in the population study. For men, those who drank the most tea had a 28 percent
lower incidence of rectal cancer and a 37 percent 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
percent and 47 percent.

Another study in Shanghai found similar associations for stomach cancer. Green tea drinkers were 29 percent less likely to get stomach cancer than nondrinkers, with those drinking the most tea having the least risk. 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 stages.

Green tea may exert an estrogen-blocking effect that is helpful in preventing
breast and uterine cancer, and another study suggests that it might
prevent the development of tumors by blocking the growth of new blood vessels. In
a review of nine studies (none of which were clinical trials) involving more than
5,600 persons, researchers found weak evidence for reduction in breast cancer
recurrence among people who consumed more than three cups of green tea every day,
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 persons, researchers saw no reduction in stomach cancer rates. Lack of benefit was also seen in a study conducted in Hawaii. Also, combining the results of thirteen observational studies, researchers found conflicting evidence for green tea’s effect on the risk of stomach cancer. However, in a small Japanese randomized trial, persons who supplemented their regular diet with an extra 1.5 grams of green tea extract per day for one year lowered their risk of recurrent colorectal polyps compared to those who took no supplement. In a review of multiple studies, including forty-three observational studies, four randomized trials and one meta-analysis (a mathematical summation of the results from several studies), researchers concluded that there was inconsistent evidence supporting green tea’s effectiveness for cancer prevention.

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.

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. 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.

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.
Furthermore, evidence from two preliminary studies in humans found changes
suggesting that soy might slightly increase breast cancer risk. Other studies in
women have found reassuring results; nonetheless, women who have had breast
cancer, or are at high risk for it, should consult a physician before taking any
isoflavone product.

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.
Because 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. 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. (PSA is a marker for prostate cancer, with higher values generally showing an increased number of cancer cells.) The results did show that the 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. 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. 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.

Folate. Observational studies have suggested that folate deficiency may predispose persons toward developing cancer of the cervix, colon, lung, breast, pancreas, and mouth. Other observational studies have suggested that folate supplements may help prevent colon cancer, especially when they are taken for many years or by people with ulcerative colitis. 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 five-year period found folate ineffective for preventing early colon
cancer. Also, in a large controlled trial involving more than 5,400 women,
supplements combining folate plus vitamins B6 and B12 taken
for seven years did not reduce the risk of a cancer compared with placebo.
However, a much smaller study involving ninety-four persons with colon polyps
(a precancerous condition) found that folate may reduce the risk of recurrent
polyps over a three-year period.

Other Proposed Natural Treatments

Some observational and intervention studies have found evidence that calcium
supplementation may reduce the risk of colon cancer. Risk reduction might continue
for years after calcium supplements are stopped. In men, however, calcium
supplements might increase risk of prostate cancer. For menopausal women, calcium
supplementation, especially when taken with vitamin D,
appears to reduce overall cancer incidence.

Some studies have connected higher vitamin D levels with a lower incidence of cancer of the breast, colon, pancreas, and prostate, and of melanoma, but overall research has yielded mixed results. In an extremely large study involving more than 36,000 postmenopausal women, supplementing the diet with 1,000 mg of calcium plus 400 IU of vitamin D daily did not lower the risk of breast cancer in a period of seven years. Based on the results of this placebo-controlled study, there does not appear to be a connection between vitamin D and breast cancer risk.

Increasing dietary fiber has long been thought to help reduce the incidence of colon polyps. However, several late studies found either little evidence of benefit or no evidence. For example, one large study enrolled almost two thousand people with a history of colon polyps and compared the ordinary American diet with a diet high in fiber, fruits, and vegetables and low in saturated fat. In 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. Lignans are converted in the digestive tract to estrogen-like substances known as enterolactone and enterodiol. Like soy isoflavones, 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 the prevention or treatment of cancer, but the supporting evidence is still extremely preliminary. Contrary to some reports, flaxseed oil contains no lignans. 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. 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 percent less likely to develop colon cancer. Similar results were seen in other observational studies performed in China, Italy, and the United States. In addition, one preliminary intervention trial also found some evidence that aged garlic may reduce risk of colon cancer.

Resveratrol is a phytochemical found in at least seventy-two
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.

One large observational study suggests that higher intake of boron may reduce the risk of prostate cancer. Provocative evidence suggests that a substance called sulforaphane, found in broccoli and related vegetables, may possess anticancer properties. 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-preventive agent; however, there is some evidence that this substance might actually increase the risk of cancer in certain circumstances. Much the same is true of the related substance diindolylmethane.

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 in a twenty-two-year period. Another study provides preliminary supporting evidence for the notion that fish oil reduces the risk of prostate cancer. However, on balance, there is still relatively little evidence that the consumption of fish oil reduces the risk of cancer.

Weak evidence hints that N-acetylcysteine treatment may help to prevent colon
cancer. Also, 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. This approach should not be
tried except under physician supervision. Vitamin K has
shown some promise for helping to prevent liver cancer
in people with chronic viral hepatitis.

Innumerable other herbs and supplements have shown minimal promise in test-tube and animal studies, including but not limited to active hexose correlated compound, 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, methyl sulfonyl methane, milk thistle, nettle, oligomeric proanthocyanidins, papaw tree bark, probiotics (friendly bacteria), royal jelly, shiitake, schisandra, and blue-green algae.

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. As noted, a large study failed to find that a diet high in fruits and vegetables reduced risk of colon polyps. Similarly, meat consumption, widely stated to increase colon cancer risk, might or might not do so (the evidence is not compelling). Data do not suggest that diets high in sugar or other simple carbohydrates increase colon cancer risk or that reducing fat in the diet reduces colon, uterine, or breast cancer risk. Higher levels of exercise might potentially help reduce the risk of various forms of cancer, especially colon cancer.

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