Antioxidants and Cancer Prevention: Fact Sheet
1. 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 otherwise might cause. Examples
of antioxidants include beta-carotene, lycopene, vitamins
C, E, and A, and other substances.
2. 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.
3. 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 (vitmain 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)
4. 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 trails can be obtained using www.cancer.gov/clinicaltrials, www.clinicaltrials.gov,
or the CRISP database at www.nih.gov.
• 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.
5. Will 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.
6. 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.
7. 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 also found in mangos, nuts, broccoli
and other foods.
References:
1) 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.
2) 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.
3) 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.
4) 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.
5) 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. |
