Antioxidants and Cancer Prevention: Fact Sheet
Key Points
- What are antioxidants?
Antioxidants are substances that may protect cells from the damage caused
by unstable molecules known as free radicals. Free radical damage may lead
to cancer. Antioxidants interact with and stabilize free radicals and may
prevent some of the damage free radicals might otherwise cause. Examples of
antioxidants include beta-carotene, lycopene, vitamins C, E, and A, and other
substances.
- Can antioxidants prevent cancer?
Considerable laboratory evidence from chemical, cell culture, and animal
studies indicates that antioxidants may slow or possibly prevent the development
of cancer. However, information from recent clinical trials is less clear.
In recent years, large-scale, randomized clinical trials reached inconsistent
conclusions.
- What was shown in previously published large-scale
clinical trials?
Five large-scale clinical trials published in the 1990s reached differing
conclusions about the effect of antioxidants on cancer. The studies examined
the effect of beta-carotene and other antioxidants on cancer in different
patient groups. However, beta-carotene appeared to have different effects
depending upon the patient population. The conclusions of each study are summarized
below.
- The first large randomized trial on antioxidants and cancer risk was the
Chinese Cancer Prevention Study, published in 1993. This trial investigated
the effect of a combination of beta-carotene, vitamin E, and selenium on
cancer in healthy Chinese men and women at high risk for gastric cancer.
The study showed a combination of beta-carotene, vitamin E, and selenium
significantly reduced incidence of both gastric cancer and cancer overall
(1).
- A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitamin
E)/ Beta-Carotene Cancer Prevention Study (ATBC) demonstrated that lung
cancer rates of Finnish male smokers increased significantly with beta-carotene
and were not affected by vitamin E (2).
- Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy
Trial (CARET), also demonstrated a possible increase in lung cancer associated
with antioxidants (3).
- The 1996 Physicians’ Health Study I (PHS) found no change in cancer
rates associated with beta-carotene and aspirin taken by U.S. male physicians
(4).
- The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene
in the prevention of cancer and cardiovascular disease among women age 45
years or older. Among apparently healthy women, there was no benefit or
harm from beta-carotene supplementation. Investigation of the effect of
vitamin E is ongoing (5).
- Are antioxidants under investigation in current large-scale clinical trials?
Three large-scale clinical trials continue to investigate the effect of
antioxidants on cancer. The objective of each of these studies is described
below. More information about clinical trials can be obtained using http://www.cancer.gov/clinicaltrials,
http://www.clinicaltrials.gov,
or the CRISP database at http://crisp.cit.nih.gov/
on the Internet.
- The Women’s Health Study (WHS) is currently evaluating the effect
of vitamin E in the primary prevention of cancer among U.S. female health
professionals age 45 and older. The WHS is expected to conclude in August
2004.
- The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking
place in the United States, Puerto Rico, and Canada. SELECT is trying to
find out if taking selenium and/or vitamin E supplements can prevent prostate
cancer in men age 50 or older. The SELECT trial is expected to stop recruiting
patients in May 2006.
- The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name. The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total cancer incidence. The PHS II is expected to conclude in August 2007.
- Will the National Cancer Institute (NCI)
continue to investigate the effect of beta-carotene on cancer?
Given the unexpected results of ATBC and CARET, and the finding of no effect
of beta-carotene in the PHS and WHS, NCI will follow the people who participated
in these studies and will examine the long-term health effects of beta-carotene
supplements. Post-trial follow-up has already been funded by NCI for CARET,
ATBC, the Chinese Cancer Prevention Study, and the two smaller trials of skin
cancer and colon polyps. Post-trial follow-up results have been published
for ATBC, and as of July 2004 are in press for CARET and are in progress for
the Chinese Cancer Prevention Study.
- How might antioxidants prevent cancer?
Antioxidants neutralize free radicals as the natural by-product of normal
cell processes. Free radicals are molecules with incomplete electron shells
which make them more chemically reactive than those with complete electron
shells. Exposure to various environmental factors, including tobacco smoke
and radiation, can also lead to free radical formation. In humans, the most
common form of free radicals is oxygen. When an oxygen molecule (O2) becomes
electrically charged or “radicalized” it tries to steal electrons
from other molecules, causing damage to the DNA and other molecules. Over
time, such damage may become irreversible and lead to disease including cancer.
Antioxidants are often described as “mopping up” free radicals,
meaning they neutralize the electrical charge and prevent the free radical
from taking electrons from other molecules.
- Which foods are rich in antioxidants?
Antioxidants are abundant in fruits and vegetables, as well as in other
foods including nuts, grains, and some meats, poultry, and fish. The list
below describes food sources of common antioxidants.
- Beta-carotene is found in many foods that are orange in color, including
sweet potatoes, carrots, cantaloupe, squash, apricots, pumpkin, and mangos.
Some green, leafy vegetables, including collard greens, spinach, and kale,
are also rich in beta-carotene.
- Lutein, best known for its association with healthy eyes, is abundant
in green, leafy vegetables such as collard greens, spinach, and kale.
- Lycopene is a potent antioxidant found in tomatoes, watermelon, guava,
papaya, apricots, pink grapefruit, blood oranges, and other foods. Estimates
suggest 85 percent of American dietary intake of lycopene comes from tomatoes
and tomato products.
- Selenium is a mineral, not an antioxidant nutrient. However, it is a component
of antioxidant enzymes. Plant foods like rice and wheat are the major dietary
sources of selenium in most countries. The amount of selenium in soil, which
varies by region, determines the amount of selenium in the foods grown in
that soil. Animals that eat grains or plants grown in selenium-rich soil
have higher levels of selenium in their muscle. In the United States, meats
and bread are common sources of dietary selenium. Brazil nuts also contain
large quantities of selenium.
- Vitamin A is found in three main forms: retinol (Vitamin A1), 3,4-didehydroretinol
(Vitamin A2), and 3-hydroxy-retinol (Vitamin A3). Foods rich in vitamin
A include liver, sweet potatoes, carrots, milk, egg yolks, and mozzarella
cheese.
- Vitamin C is also called ascorbic acid, and can be found in high abundance
in many fruits and vegetables and is also found in cereals, beef, poultry,
and fish.
- Vitamin E, also known as alpha-tocopherol, is found in almonds, in many
oils including wheat germ, safflower, corn, and soybean oils, and is also
found in mangos, nuts, broccoli, and other foods.
Selected References
- Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention
trials in Linxian, China: supplementation with specific vitamin/mineral combinations,
cancer incidence, and disease-specific mortality in the general population.
J Natl Cancer Inst 1993;85:1483–91.
- The Alpha-Tocopherol, Beta Carotene Cancer Prevention
Study Group. The effects of vitamin E and beta carotene on the incidence of
lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029–35.
- Omenn GS, Goodman G, Thomquist M, et al. The beta-carotene
and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high
risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54(7
Suppl):2038s–43s.
- Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner
B, Cook NR, et al. Lack of effect of long-term supplementation with beta carotene
on the incidence of malignant neoplasms and cardiovascular disease. N Engl
J Med 1996;334:1145–9.
- Lee IM, Cook NR, Manson JE. Beta-carotene supplementation
and incidence of cancer and cardiovascular disease: Women’s Health Study.
J Natl Cancer Inst 1999;91:2102–6.
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