bHealthyUSA Featured Article - Antioxidants
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 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.
Key Points
Antioxidants protect cells from damage caused by unstable molecules known as
free radicals (see Question 1&3).
Laboratory and animal research has shown antioxidants help prevent the free
radical damage that is associated with cancer. However, results from recent studies
in people (clinical trials) are not consistent (see Question 2).
Antioxidants are provided by a healthy diet that includes a variety of fruits and
vegetables (see Question 4).
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.
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 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.
Key Points
Antioxidants protect cells from damage caused by unstable molecules known as
free radicals (see Question 1&3).
Laboratory and animal research has shown antioxidants help prevent the free
radical damage that is associated with cancer. However, results from recent studies
in people (clinical trials) are not consistent (see Question 2).
Antioxidants are provided by a healthy diet that includes a variety of fruits and
vegetables (see Question 4).
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.
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