Melatonin, long
known to insomniac Americans as an over-the-counter
sleep aid, is now being studied as a way to prevent
and treat breast and other cancers.
Dubbed the "hormone of darkness," melatonin is a
hormone that is made by the brain's pineal gland at
nighttime. This summer, researchers at Brigham and
Women's Hospital led by pidemiologist Dr. Eva
Schernhammer showed that women who produced the
lowest levels of melatonin had a 70 percent higher
chance of getting breast cancer than those with the
highest levels.
Schernhammer’s
group had previously shown that women who work at
night are at higher risk of both breast and colon
cancer. Light at night can shut off melatonin
production.
A Finnish study
to be published this fall explores whether women who
sleep 9 hours or more a night -– and hence produce
more melatonin -– are at lower than average risk of
breast cancer.
A co-author of
that study, cancer epidemiologist Richard Stevens of
the UConn Health Center in Farmington, Conn., said
that breast cancer rates are much higher in
industrialized countries, where, among other things,
people use artificial light at night, which
suppresses melatonin production.
“We can’t say
yet, but the evidence is accumulating that
light-at-night, and the consequent decrease in
melatonin, may be a major driver of breast cancer,”
Stevens said. From an evolutionary point of view,
melatonin may have developed as a signal to tell
animals when to breed. In sheep, melatonin levels
rise in the fall as the nights get longer, and ewes
become fertile -- perhaps as nature’s way of
insuring that when they give birth four months
later, the weather will be balmier.
Melatonin is
also an important regulator of the circadian clock
in the brain, which keeps the body on a regular
cycle of day and night. Light, whether from the sun
or electric lights, suppresses melatonin production.
But when light
disappears, and darkness falls, there’s a cascade of
nerve signals from the eye to the pineal gland,
which then starts making melatonin.
That's why
melatonin has been popularized as a sleep aid. But a
government study in 2004 found the melatonin pills
on the market had limited effectiveness. A more
recent study from MIT suggests that the problem may
simply be dosing: The pills that are currently sold
in healthfood stores are many times too strong. A
dose of only .3 milligrams helps people fall asleep
faster, according to a study led by Richard Wurtman,
director of MIT's Clinical Research Center.
Frustrated by
the high rates of breast cancer in industrialized
countries, Stevens of UConn hypothesized back in the
late 1980s that light-at-night might drive cancer
and that melatonin might protect against it.
“We know that if
you take out the pineal gland in animals, that
removes all melatonin, and then if you inject cancer
cells, the cancer growth rate increases,” said
Steven Lockley, a neuroscientist at Brigham and
Women’s, who is now studying blind women to see if
they have higher than normal levels of melatonin,
and whether they get less breast cancer. “We know
that when you put an animal in constant light, that
also stops all melatonin production, and you get a
similar response. And if you then treat an animal
with melatonin, you can slow down the cancer rate.”
Researchers are just now starting to look at the
treatment potential for melatonin.
At the Bassett
Research Institute in Cooperstown, NY, Dr. David
Blask, a senior research scientist, reported at a
cancer meeting this summer that melatonin can “put
cancer cells to sleep” by blocking their ability to
soak up linoleic acid, which makes cancer cells grow
rapidly. In animal studies, Blask said he has found
that cancer cell growth is slower at night, when
melatonin is highest, and faster during the day. He
also found that adding melatonin to human breast
cancer cells grown in rats can slow the cancer's
growth.
In other animal
studies, Steven Hill, vice chairman of structural
and cellular biology at Tulane University in New
Orleans, has found that melatonin binds to receptors
on both normal and breast cancer cells. Once it
lands on a receptor, he said, it acts on chemical
signals inside the cell to suppress estrogen, which
drives many breast tumors. “We can prevent 85
percent of mammary tumors in our rats with a
combination of melatonin and retinoid [vitamin A],”
he said.
In Europe,
studies of people with cancer who are given
melatonin are also promising, though preliminary.
Melatonin appears able to not only slow cancer
progression and improve survival in advanced cancer
patients, but to protect healthy cells from the side
effects of chemotherapy and radiation, said Dr. Fade
Mahmoud, a clinical instructor at the University of
South Dakota School of Medicine who published a
review of the studies this summer.
Spanish
researchers have shown that melatonin acts in human
breast cancer cells much like drugs called aromatase
inhibitors, such as Arimidex, Aromasin and Femara.
This means it can prevent the body from converting
the hormone testosterone into estrogen.
Italian researchers, in a long series of human
studies, have shown that melatonin, which appears to
have little toxicity, can boost survival at least
modestly in some people with melanoma and cancers of
the lung, breast, kidney and other organs.
These studies
“sound intriguing,” said Dr. Mark Pegram, director
of the Women’s Cancer Program at the Jonsson
Comprehensive Cancer Center at UCLA. “But obviously
more experimental studies are needed to evaluate
whether or not melatonin may play a role in breast
cancer growth regulation.”
Spurred by the
positive results, American researchers are starting
to pay attention to melatonin. With colleagues at a
cancer research center in Zion, Ill., Dr. William
Hrushesky, a senior clinician-investigator at the
Dorn VA Medical Center in Columbia, S.C., is doing
a randomized, double-blind study with melatonin plus
chemotherapy to see if melatonin helps lung cancer
patients.
While it’s too
soon to rush out and buy over-the-counter melatonin
to fight cancer, it is a good idea to “live a
melatonin-friendly lifestyle,” said Stevens of UConn.
That means going
to bed earlier if you’re a night owl, making sure
the bedroom is dark and keeping the light dim in the
bathroom if you make nightly trips there.
If you're a
shift worker, ask your employer to explore changing
the room lighting, more closely simulating normal
night.
“The longer you stay in the dark," Stevens said,
"the more melatonin you’re putting out.”
Judy Foreman’s column appears every other week. Past
columns are available on
www.myhealthsense.com.
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Breast Cancer