Here's some important information for our molers. Your friend, lillian
Investigators conducting the Beta Carotene and Retinol Efficacy Trial
(CARET), a large study of the combination of beta carotene and vitamin A as
preventive agents for lung cancer in high-risk men and women, terminated
the intervention last week after an average of four years of treatment and
told the 18,314 participants to stop taking their vitamins. Interim study
results indicate that the supplements provide no benefit and may be causing
harm.
Investigators in another trial, the Physicians' Health Study, said today
that their study of 22,071 U.S. male physicians ended on schedule, Dec. 31,
1995, after more than 12 years of treatment. The study showed no
significant evidence of benefit or harm from beta carotene on cancer or
cardiovascular disease.
Both studies have been funded by the National Cancer Institute (NCI) of the
National Institutes of Health (NIH). The Physicians' Health Study was also
funded by NIH's National Heart, Lung, and Blood Institute.
CARET's lead investigator, Gilbert S. Omenn, M.D., Ph.D., of the Fred
Hutchinson Cancer Research Center and the University of Washington School
of Public Health in Seattle, explained that regular independent review of
the study data showed that lung cancer incidence was unlikely to be reduced
by the daily intervention of 30 milligrams (mg) of beta carotene and 25,000
international units (IU) of vitamin A by the scheduled end of the study and
that there was a substantial possibility that the supplements might be
harming the participants, who are smokers, former smokers, and men exposed
to asbestos on the job.
CARET results to date, including 388 people diagnosed with lung cancer and
974 deaths from all causes, showed 28 percent more lung cancers and 17
percent more deaths in participants taking beta carotene and vitamin A.
While these interim results are not significant evidence of harm from a
statistical standpoint, they are similar to the results of the
Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Trial
published in 1994, which showed 18 percent more lung cancers and 8 percent
more deaths in the portion of the 29,133 male smokers in Finland who took
20 mg of beta carotene daily for five to eight years.
Letters asking the 18,314 CARET participants to stop taking their vitamin
supplements or placebos were mailed Jan. 13. Investigators plan to follow
the participants for at least five more years to determine the long-term
effects of the intervention, which was interrupted 21 months early. Omenn
said that CARET data also raise the possibility that former smokers, who
comprised 34 percent of the participants when recruited, may respond more
favorably to vitamin A and beta carotene than current smokers, but that the
data are too limited to draw any conclusions at this time. Results from the
Physicians' Health Study, the trial of 22,071 U.S. male physicians taking
50 mg of beta carotene or a placebo every other day for 12 years, showed
that beta-carotene supplements had no significant effect -- positive or
negative -- on cancer or cardiovascular disease in this population of
mostly nonsmokers (11 percent are current smokers while 51 percent smoked
at some time in their life). Charles H. Hennekens, M.D., Dr.P.H., of
Harvard Medical School and Brigham and Women's Hospital, Boston, headed
this study, which showed in 1988 that low-dose aspirin reduces the risk of
a first heart attack.
In response to the lack of benefit seen in CARET, the Physicians' Health
Study, and the ATBC trial, another ongoing trial is removing beta carotene
supplements from its intervention. The Women's Health Study, a trial of
40,000 female health professionals, headed by Julie Buring, Sc.D., of
Harvard Medical School and Brigham and Women's Hospital, began in 1992. The
study will continue to evaluate every-other-day doses of 600 IU of vitamin
E and 100 mg of aspirin or placebos.
Public Health Concern
The results of CARET and the Physicians' Health Study provide strong
evidence of no benefit from beta carotene supplements and raise questions
about their safety for the general public. "The National Cancer Institute
has never had a recommendation for Americans to take supplements," said
Peter Greenwald, M.D., Dr.P.H., director of NCI's Division of Cancer
Prevention and Control. "The best advice for smokers who want to reduce
their risk of lung cancer is still the most direct: Stop smoking. Results
from CARET and the ATBC Trial do suggest, however, that smokers should
avoid beta carotene supplements."
Omenn underscored the "quit smoking" message by praising the many CARET
participants who were smokers at the beginning of the trial and who have
quit during the study. Twenty-two percent of those who smoked at the
beginning of the trial have quit.
Greenwald continued, "For all Americans who wish to reduce their risk of
lung and other cancers, a low-fat diet with plenty of fruits, vegetables,
and grains is the choice to make. These studies show nothing to suggest
that smokers or nonsmokers might benefit from beta carotene supplements."
Hennekens concurred, noting that "taken together, the results of CARET,
ATBC, and the Physicians' Health Study clearly tell us that beta-carotene
supplementation is not a magic bullet -- it can neither substitute for a
good diet nor compensate for a bad one."
NCI Director Richard Klausner, M.D., praised the work of the researchers
and participants of CARET and the Physicians' Health Study, as well as
applauding the process of science. "Medicine and public health must be
based, whenever possible, on evidence. These trials discussed today provide
that essential evidence... While the results are disappointing, the
research process, I believe, is working."
CARET Background and Study Design
The study is being conducted in six areas of the United States with a
principal investigator at each site and Omenn coordinating the trial. The
six investigators and cities participating in CARET are: Gary E. Goodman,
M.D., Fred Hutchinson Cancer Research Center, Seattle, Wash.; Barbara G.
Valanis, Dr.P.H., Kaiser Center for Health Research, Portland, Ore.; James
P. Keogh, M.D., University of Maryland at Baltimore, Baltimore, Md.; John
R. Balmes, M.D., University of California-San Francisco, San Francisco,
Calif.; Frank Meyskens, Jr., M.D., University of California-Irvine, Irvine,
Calif.; Mark R. Cullen, M.D., Yale University School of Medicine, New
Haven, Conn.
The study is comprised of two groups: 14,254 current and former smokers
with a long history of smoking and 4,060 asbestos-exposed individuals. The
total number of participants is 18,314.
Recruited in Seattle, Portland, and Irvine were 14,254 men and women ages
50 to 69 who are current smokers or are smokers who had quit within six
years of enrolling in the study. Smokers and former smokers must have had a
smoking history of at least 20 pack years (one pack per day for 20 years or
two packs for 10 years, etc). These participants are 56 percent male
(7,965) and 44 percent female (6,289) and had an average of 50 pack years
of smoking. About 34 percent were former smokers when they joined the
study. All participants were counseled to quit smoking during their visits
to the study centers. The racial distribution of the participants is 95
percent white, 2 percent African-American, 1 percent Hispanic, and 2
percent Asian or other.
At five of the six centers (Irvine, Calif. excluded), 4,060 men ages 45 to
69 years who had been exposed to asbestos while at work were enrolled in
CARET. These participants had to have extensive occupational asbestos
exposure beginning at least 15 years earlier, determined by either a chest
X-ray that showed asbestos exposure or employment for more than five years
in trades that carry a high risk of exposure to asbestos: plumbers and
pipefitters, steam fitters, shipyard boilermakers, nonshipyard
boilermakers, shipyard electricians, shipscalers, insulators, plasterboard
workers, or sheetmetal workers. In addition, they had to be either current
smokers or had to have quit smoking within the last 15 years. One- half the
CARET participants in both groups took a combination of beta carotene and
vitamin A and one-half took inactive placebos. Beta carotene is an
antioxidant, a compound that may prevent cancer-causing substances from
damaging DNA. Epidemiologic studies have linked high dietary intake of beta
carotene and high serum levels of this micronutrient to a reduced risk of
cancer, particularly lung cancer. Vitamin A was chosen for study because it
is known to play a part in cell differentiation, a process of "maturing"
cells that helps prevent them from inappropriate growth, such as the
uncontrolled cell growth that is seen in cancer. Vitamin A (retinol) and
its analogues have been shown to be effective in preventing cancers in
animals exposed to chemicals like those in cigarette smoke. Beta carotene
and vitamin A were given as a combination under the hypothesis of a
potentially favorable interaction between the two compounds. The dose of
beta carotene in CARET was 30 mg/day, which is equivalent to 50,000 IU of
vitamin A or about five medium-sized carrots. Vitamin A was given as
retinyl palmitate in a dose of 25,000 IU.
Physicians' Health Study Background and Study Design
The Physicians' Health Study was conducted nationwide among 22,071 U.S.
male physicians ages 40 to 84 years, 11 percent of whom were current
smokers and 51 percent of whom had smoked at some time in their life when
recruited to the study in 1982.
The participants took either 50 mg of beta carotene every other day or a
placebo and 325 mg of aspirin or a placebo on the alternate day. The
randomized aspirin component ended early, after five years, primarily
because a benefit of aspirin on risk of first heart attack was found (a 44
percent reduction was seen in those taking aspirin). The beta carotene
treatment continued until its scheduled termination on Dec. 31, 1995.
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