VOLUME 34 • N UMBER 6
APRIL 2009
Putting the joie de vivre back into health
The eat-your-peas mode of staying healthy is changing to include
chocolate, sleep, and a few other things most people enjoy.
N
and higher blood levels of omega-3 fats. Indeed, temperate tippling has been associated
with everything from greater bone density to
less risk for Alzheimer’s disease and vascular
dementia.
Moderation gets mentioned rather immoderately in the pro-alcohol medical literature because drinking too much is patently
ruinous. Triglycerides and blood pressure
go up. Binge drinking can lead to stroke.
The myriad troubles associated with
alcoholism don’t need to be recounted
here. Moderation is flexibly defined, but
the American Heart Association
guidelines are often cited: for men,
one to two drinks a day; for women, just one.
The limit is lower for women because they
tend to be smaller and break down alcohol
more slowly than men. A drink is defined as a
12-ounce beer, 4 ounces of wine, or 1.5 ounces
of 80-proof liquor.
Women do need to worry about alcohol increasing breast cancer risk. Alcohol may drive
up estrogen levels, and estrogen seems to play
an integral part in the development of many
breast cancers. Epidemiologic studies have
consistently found an association between
alcohol consumption and breast cancer risk,
although at moderate amounts (the drink-aday level), the risk is small. The good news:
folic acid may help offset the breast cancer
Alcohol
Dozens of studies have shown that moderate risk posed by alcohol, so women who drink
alcohol consumption protects against heart are encouraged to get an extra 400 microdisease and stroke. Drinking increases “good” grams per day.
HDL cholesterol, reduces factors in blood
that make it more likely to clot, and may di- Chocolate
rectly affect blood vessels, keeping the linings Woody Allen saw it coming with his joke in
smooth and pliable and thus less vulnerable Sleeper about researchers deciding that hot
to atherosclerosis. European researchers re- fudge was good for us after all. A steady stream
ported interesting findings late last year that of studies has won chocolate cardiovascular
show a connection between alcohol intake laurels by showing that it improves blood
o one likes to be nagged, but that’s
often what health advice seems to do.
There are all those don’ts (as in smoke,
eat too much, gain weight). And the dos (exercise, eat fruit and vegetables) are predictable,
even for people who don’t mind them. Live
longer, live healthier, you say? Okay, but what
a chore and a bore!
Lately, however, health researchers are
reporting results that suggest maybe we
can have our health and enjoy ourselves, too. Recent studies have elevated coffee to health-drink status by
linking it to a reduced risk of dementia and Parkinson’s disease. Dozens of
findings have shown that alcohol and chocolate may have cardiac benefits. Sex, sleep, and
a social life seem to have all-around benefits.
Never has high living looked quite so
healthful, although it’s high living on a leash.
The permission to indulge almost always
comes with a reminder about doing everything in moderation.
So here is a rundown of research we ran
across thumbing through our dog-eared copies of The Archives of Hedonism and Health
(fine, the journal name is fictitious, but the
research cited below is not). Enjoy and be
healthy—in that order!
INSIDE
Surgery for pancreatic
cancer
The Whipple procedure
has gotten a lot safer. . . 4–5
Nutrition insurance
Is the multivitamin still
a good policy? . . . . . . . 6 –7
By the way, doctor
Calorie cutbacks and
memory gains; omega-3s
and bleeding. . . . . . . . . . . 8
In future issues
Falls
Gluten
Donating your body
to science
What’s new
Workout Workbook:
9 complete workouts to
help you get fit and healthy
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2 | Harvard Health Letter
April 2009
flow through arteries that supply the heart
and the brain (which Allen said is his
second favorite organ). Chocolate’s winning ways continued last year. Harvard
researchers found that two weeks of
enhanced chocolate intake (now that’s our type of
study!) quickened blood flow
through the middle cerebral
artery. And Italian researchers reported a possible connection between eating dark
chocolate and low levels of C-reactive
protein, a marker for inflammation.
Not every study has been a thumbs up:
researchers at the National Institutes of
Health concluded that chocolate did not
decrease blood pressure or improve insulin sensitivity in a two-week study of people with high blood pressure. Moreover,
the chocolate-as-healthful dream needs a
couple of reality checks. The most likely
explanation for chocolate’s good effects
is that cocoa beans contain substances
called flavonols (specifically, catechin
and epicatechin, which are also found in
tea) that stimulate production of nitric
oxide, a chemical that relaxes blood vessels. In the studies cited above, researchers have used “flavonol-rich” chocolate.
But typically, the processing of cocoa
beans into chocolate removes flavonols.
Dark chocolate may have more flavonols
than other types, but you can’t go just by
darkness. Some companies have started
to market products advertised as preserving the cocoa bean’s flavonol content
(for example, the Cocoavia bars made by
Mars, a company that has funded a lot
of the pro-chocolate research).
Another caveat: the sugar and fat
content of chocolate candy translates
into calories (over 200 in a 3.5-ounce
bar of expensive dark chocolate). And
some of the fat in many chocolate bars is
the unhealthful saturated variety.
Coffee
For the health conscious, a cup of coffee was once a somewhat perilous pleasure. Early studies showed a connection
between coffee and heart attack, a worry
that seemed to be validated by coffee’s
ability to quicken the pulse. Some other
studies cast the gloomy shadow of cancer
risk.
But the cancer research was flawed or
overturned by more definitive findings.
Not all the evidence has been exculpatory,
however. A Harvard study published
late last year found no overall association between caffeine consumption and breast cancer risk, but there
were hints of a connection in women
with a history of benign breast disease
and those whose tumors were estrogenand progesterone-receptor negative.
Meanwhile, the coffee–cardiovascular
disease research has done an about-face:
now the gist is that coffee drinkers seem
to be less likely to have heart attacks
and strokes and develop diabetes than
nondrinkers. The caffeine in coffee does
constrict blood vessels (that’s why it can
help with headaches caused by vessels
that have dilated) and may increase your
heart rate a little, but those are transitory effects. Coffee has other ingredients
(specifically, phenolic compounds) that
seem to cancel out whatever negative
effects chronic exposure to caffeine might
have. Those other ingredients might explain why decaffeinated coffee has shown
benefits similar to the caffeinated version
in several studies.
Study results going back almost
10 years indicate that coffee drinking
may tamp down the risk of developing
Parkinson’s disease. No one is sure why,
although it’s been suggested that caffeine
affects receptors in the basal ganglia, the
part of the brain most damaged in Parkinson’s. Other studies are brewing hopes that coffee may affect
our brain cells in ways that
diminish risk for dementia
and Alzheimer’s disease.
The good healthkeeping
seal of approval for coffee comes with
cautionary notes. Pregnant women are
still advised to limit, if not avoid, caffeine
intake, although the American College
of Obstetricians and Gynecologists’ position is confusing. Its patient brochure
says “some studies suggest drinking three
or more cups of coffee per day may increase the risk of miscarriage,” but adds
“there is no proof that caffeine causes
www.health.harvard.edu
miscarriage.” Another caution: unfiltered coffee—which includes coffee
drinks made with espresso—may increase “bad” LDL levels because some
harmful substances in the coffee don’t
get filtered out. There’s nothing wrong
with the occasional latte or cappuccino,
but overdoing it may mean a return
to the bad old days when coffee was
cardiovascularly suspect.
Sex
Obviously sexual arousal and orgasm
is a source of great pleasure and a sense
of well-being, but even after the immediate glow fades, there may be residual health benefits. Sexual activity can
cause heart attacks, but it’s been estimated that chances are only one in a
million that a man who has had a heart
attack will have another during or immediately after sex. Meanwhile, other
research has suggested that frequent
sexual intercourse (twice a week) is associated with reduced heart attack risk,
even after making the
statistical adjustments
necessary to account
for the fact that men
who have sex that often are healthier over
all. Conventional
sexual activity revs
up the metabolism, but only so far: orgasms, minute for minute, create the
same exercise workload as walking at
a pace of three miles per hour. The cardiovascular demands of sex have been
compared to walking up two flights of
stairs. Even if sex isn’t great aerobic
exercise, exercise may make for better
sex: several studies have shown that
moderate exercise increases genital
response to erotic stimuli in women.
Marvin Gaye sang about it, but you
can also find bits and pieces of evidence
in the medical literature of the power of
sexual activity to fix medical problems.
Several years ago, an Israeli neurologist published a case report about two
male patients whose headaches went
away after sexual intercourse or orgasm
(although sexual activity as a cause
of headaches is far more common).
www.health.harvard.edu
Researchers have reported that women who have intercourse regularly are
more likely to have regular menstrual
cycles. And sex may be a pretty good
germ fighter. Several years ago, German investigators reported that white
blood cell counts went up in men
after sexual activity (in this
case, masturbation-induced
orgasm). That’s in keeping
with other research suggesting that sex gives the immune
system a boost.
Granted, these studies are too small
or short to be anything but speculative
and suggestive. The fact is that much
of the research into health and sexual
activity has focused on how illness adversely affects sexuality, a worthy topic,
but it might be revealing to turn the
tables and pay a little more attention to
the vice versa: how sexual activity may
have ameliorating effects on illness.
Sleep
We’re resting easier (sometimes longer)
these days because of the laurels that
sleep is winning for its health benefits
—or, more precisely, because of the
evidence of all the bad things that can
happen when we don’t get enough of
it. Several epidemiologic studies—the
kind that involve following thousands
of people over many years—have
shown that “short sleepers” put on
more pounds than people who sleep
seven to eight hours a night, which
is the amount that seems optimal for
most adults. Other studies have linked
skimping on sleep to the high-risk pool
for heart attacks, diabetes, and early
death. The risks are more pronounced
for people who sleep less than five
hours a night, but the danger seems to
extend to those averaging less than six.
It’s easy to poke holes in epidemiologic
evidence, but short-term experiments
in sleep deprivation have lent credence
to these findings. When healthy volunteers stay awake for long stretches, it
wreaks hormonal havoc: levels of cortisol, a stress hormone, go up, and leptin
and ghrelin, hormones that influence
appetite, get thrown out of whack.
Of course, lack of sleep has a very
direct effect on the brain, influencing
memory, mood, and attention. We’ve
all experienced grogginess after not
getting enough sleep. Dr. Charles A.
Czeisler, a Harvard sleep expert
who has campaigned for limiting the working hours of
medical residents, says averaging four hours
of sleep a night
for four or five
days results in the
same level of cognitive
impairment as being legally drunk.
Can you sleep too much? Several of
the epidemiologic studies of sleep show
that long sleep (nine hours nightly or
more) is associated with just as many
health problems as short sleep, if not
more. But it’s probably more often the
case that an underlying illness (depression is a prime example) causes people to sleep more, not the other way
around.
Social life
We could all use a little help from our
friends, but just having them may also
help us stay healthier. A slew of studies has shown an association between
social networks and good health. Cognitive decline, high blood pressure,
the risk of dying after a heart attack—
they’ve all been linked to social isolation and loneliness. Sorting out cause
and effect is difficult. Ill-health itself
can strain social ties, although it’s also
true that coworkers,
friends, and relatives tend to rally
around people
who have strong
social networks
prior to getting
ill. Teasing apart
the objective (not
having someone to take you to the
doctor, for example) and subjective
(being lonely) aspects of isolation is
yet another conundrum. Regardless,
tending to friendships, family, and
community life is a good habit to cultivate for health and other reasons.
April 2009
Harvard Health Letter |
3
The Whipple procedure
Better outcomes for pancreatic cancer surgery.
P
ancreatic cancer has been in the
public eye lately because it has
afflicted several prominent people, including Supreme Court Justice
Ruth Bader Ginsburg, Apple CEO Steve
Jobs, actor Patrick Swayze, and Randy
Pausch, a computer science professor
at Carnegie Mellon University whose
inspirational last lecture became a
YouTube sensation and, as a book, a
national best seller.
It’s odd that the disease would strike
so many famous people at about the
same time, because pancreatic cancer
is fairly uncommon. Nearly 38,000
Americans were diagnosed with the disease last year, a fraction of the 215,000
who will be diagnosed with lung cancer. The media attention isn’t hard to
fathom, though. It’s morbid interest: no
other common cancer has such a poor
prognosis. Only about 5% of those
diagnosed with pancreatic cancer are
alive five years later, in contrast to about
66% of colon cancer patients and 90%
of female breast cancer patients. For a
variety of reasons—screening, earlier
diagnosis, better treatment—cancer
isn’t the proverbial death sentence it
once was. For many, it is a survivable
(if harrowing) condition that can be
lived with for many years in relative
good health. Pancreatic cancer stands
out as a throwback.
But one bright spot in pancreatic
cancer treatment is improved results
for the Whipple procedure, the operation most often used to treat the disease.
In the 1970s, over 15% of the patients
who had the procedure died during
the operation or shortly afterward. Improvements in surgical technique, anesthesia, and postoperative care have
driven that rate into the low single
digits at some hospitals, and the fiveyear survival rate after the operation
may be as high as 20%. Studies have
consistently shown that results are better at hospitals where many Whipples
are done, and the operation is held up
as an example of why steering patients
4 | Harvard Health Letter
April 2009
to high-volume centers for complex
surgeries and treatments might be one
way to improve the quality of health
care and treatment outcomes.
One head, two hats
A healthy pancreas is spongy, yellowishtan, and about seven inches long. It has
a creaturely shape, with a large head
that nestles into a loop of the first part
of the small intestine (the duodenum),
a longish body that squeezes behind
the stomach, and a narrower tail that
reaches the spleen (see the illustration
on the next page). Physiologically, the
pancreas wears two hats. It contains
exocrine tissue that produces digestive
enzymes, which are transported via
ducts to the small intestine, and endocrine tissue that produces hormones,
including insulin and glucagon. Over
90% of pancreatic cancers come from
the exocrine part, and most of them are
ductal adenocarcinomas—cancers that
form in the lining of the organ’s elaborate ductwork.
Some pancreatic cancers are caught
early, discovered incidentally on computed tomography (CT) scans and
other imaging studies ordered for unrelated reasons. That’s apparently what
happened in Ginsburg’s case.
But for the most part, pancreatic
cancer is diagnosed after someone has
symptoms, which typically include abdominal pain, weight loss (common
with cancer but especially so with pancreatic cancer), and jaundice, a yellowing of the skin and the whites of the
eyes from a buildup of bilirubin in the
blood, which can occur when a pancreatic tumor impinges on the common
bile duct. A major reason pancreatic
cancer is so lethal is that the cancer
grows and spreads long before it causes
any symptoms.
Surgical candidates
At the time of diagnosis, about 40% of
pancreatic cancer patients have cancer
that has already spread (metastasized)
extensively outside the organ. Surgery
isn’t an option once that has happened.
Another 40% of patients have “locally
advanced disease”: the cancer hasn’t
metastasized, but it may have adhered
to or invaded adjacent structures. The
pancreas wraps around two large blood
vessels, the superior mesenteric vein
and artery. If the cancer gets intertwined with those blood vessels, that
may preclude surgery.
Locally advanced pancreatic cancer can be treated with radiation and
chemotherapy, but the median survival time is eight to 12 months. It’s even
shorter for people whose cancers have
metastasized.
That leaves about 20% of pancreatic cancer patients with tumors that
are, in the words of cancer specialists,
“resectable”—that is, they can be treated surgically. Most of these tumors are
confined to the head of the pancreas or
its extension, the uncinate process, and
the Whipple procedure is the preferred
operation. By the time the cancer is in
the body or tail of the pancreas, it’s usually too late to operate, although that’s
not always the case.
The Whipple procedure
Pancreaticoduodenectomy, the formal
name for the Whipple procedure, is a
mouthful, so even doctors prefer the
eponym. The procedure is named for
Dr. Allen O. Whipple, the first American surgeon to perform the operation
in 1935.
Because resectable pancreatic cancer
is limited to the head of the pancreas
in most cases, you might think that the
operation to remove it would involve
taking out just that part of the pancreas.
But the head of the pancreas is structurally tied in to other organs and ducts,
and it shares a common blood supply
with them, so to remove it requires a
much more extensive operation, namely
the Whipple. A Whipple involves removing the head of the pancreas, the
duodenum, the common bile duct, the
www.health.harvard.edu
gallbladder, and often part of the stom- more productive pancreases. Leaks cited study published in The New Engach (see illustration). Surgeons then seal can be treated with slender drains that land Journal of Medicine several years
off the end of the small intestine and channel the juices out of the body so ago, the death rate at low-volume hospireattach what’s left of the bile duct, pan- they don’t collect inside the abdomen. tals (those where less than one Whipple
creas (body and tail), and stomach.
Dr. Fernández-del Castillo says a CT a year was performed, on average) was
Patients typically spend a week in scan can help doctors decide if a leak four times higher (16.3% vs. 3.8%) than
the hospital. The recovery at home is serious and needs treatment.
at high-volume hospitals (more than 16
can be slow and fairly painful,
procedures a year).
so painkillers of some kind
The same high-volume–
The Whipple procedure for pancreatic cancer
are usually needed. Initially,
better-outcome math seems to
To the liver
1
Whipple patients can eat only
apply to surgeons. According
very small amounts of food
to
one study, operative morGallbladder
that are very easy to digest,
tality rates varied by a factor
and they may need to take
of nearly four depending on
Stomach
pancreatic enzymes to help
the number of Whipples perResection
with digestion, particularly of
formed by the surgeon, even
Common
fatty foods. Diarrhea can be a
at a high-volume hospital.
bile duct
problem that makes getting out
of the house difficult. But, reStill an uphill battle
Body
and
tail
markably, the rearranged and
The post-Whipple prognoof pancreas
sis is brightest for patients
plumbed digestive tract manTumor
whose cancers have not
ages to recover in two to three
inside head
Resection
spread to nearby lymph
months. “Last night I had steak
of pancreas
and steak fries, and I’m doing
nodes. For these “node negaDuodenum
pretty well,” a 37-year-old pative” patients, the five-year
(first part of the
Jejunum
survival rate is 25% to 30%.
tient told us in early February.
small intestine)
For node-positive patients,
He had his Whipple operation
it’s only about 10%. Regardin October 2008.
One variation on the Whipless of their lymph node statShortened pancreas
2
ple keeps the stomach intact.
us,
most Whipple patients
(head removed)
will get radiation therapy,
Pylorus-preserving Whipples
chemotherapy, or both, to
(the pylorus is the muscular
Hepatic duct attached
opening of the stomach that
improve these odds, but can(gallbladder and
attaches to the duodenum) recer specialists haven’t settled
common bile duct
duce surgical time and, theoon the right combination nor
removed)
retically, improve digestion
precisely which drugs should
and nutrition. Surgeons at
be used (there have been enJohns Hopkins Hospital favor
couraging results for a drug
the pylorus-preserving procecalled gemcitabine).
dure, but Dr. Carlos FernándezBut another sobering way
Smaller stomach
del Castillo, a surgeon at
to
view those survival per(bottom portion
removed)
centages is to consider the
Harvard-affiliated MassachuEnd of jejunum sealed off
setts General Hospital, said
larger percentage of Whipple
(duodenum removed)
surgeons there don’t do them
patients who don’t make it to
for two reasons. First, studies
the five-year mark. Randy
haven’t shown any long-term
Pausch is an example. He was
benefit. Second, patients are more likely More is better
diagnosed in the summer of 2006, had
to need intravenous feeding and stay in Many studies have shown that the out- a Whipple and follow-up radiation and
the hospital longer.
comes for an operation tend to be better chemotherapy. Pausch was 47 when he
The most common complication at hospitals where those operations are died in July 2008. The improvements in
immediately after surgery is leakage performed often. This commonsensical the Whipple operation are a welcome
of pancreatic juices from the remnant relationship seems to be especially true development, but it’s a relatively small
of the pancreas. This may be more of of the Whipple procedure, probably be- step in the long, uphill battle against
a problem for patients with healthier, cause of its complexity. In one frequently pancreatic cancer.
www.health.harvard.edu
April 2009
Harvard Health Letter |
5
Vitamins: Benefit of the doubt vs. doubts about benefit
Negative studies have piled up, but are they a fair test?
G
ood news about vitamins is hard
to find these days. Headline
after headline—including a few
in this newsletter—blare negative results. B vitamins don’t prevent heart attacks. Vitamin E doesn’t benefit people
with Alzheimer’s disease. Vitamins A,
C, and E—no cancer protection there.
Lack of benefit is one thing. But
mixed in with the null findings are a
few that suggest large doses
of vitamins might cause
some real harm. One of the
first came in 1994, when
results from a high-profile
Finnish study linked beta carotene,
a form of vitamin A, to an increased
risk of lung cancer in male smokers. Several years later, high intake of
retinol—another form of vitamin A
—was linked to hip fractures.
More recently, folic acid has come
under some suspicion. Studies have
identified a possible connection between high intake of this B vitamin
and increased risk of cancer, particularly colon cancer. And because flour
and other grain products are fortified
with folic acid, most of us are consuming more folic acid than we realize.
Taking large, “megadoses” of individual vitamins has been a dubious
proposition for quite some time (although exactly what constitutes a megadose is ill-defined). There are, though, at
least two notable exceptions. First, pregnant women—indeed, all women of
childbearing age—should get extra folic
acid (400 micrograms daily) to protect
against birth defects. Second, there’s
growing evidence that most Americans—particularly those in the northern
two-thirds of the United States—would
benefit from getting between 800 international units (IU) and 1,000 IU of
vitamin D daily, which is twice as much
as the official recommendation.
What is new is that the multivitamin
has become a harder call these days.
For years, even the most mainstream of
doctors have been comfortable recom6 | Harvard Health Letter
April 2009
mending them. They’re not hugely expensive: taking a Centrum Silver every
day for a year costs about $30. They’re
an easy way to fill in the nutritional
gaps left by our less-than-ideal eating
patterns. And where we don’t have gaps,
they supply modest surpluses—a nice
hedge just in case extra amounts of
some vitamins (and minerals) do turn
out to have health benefits.
But as the negative findings of studies of vitamins
have piled up, there’s been
some pulling back. Several
years ago, a conference of experts convened by the National
Institutes of Health came to the conclusion that there was insufficient evidence
to recommend multivitamins. Last year,
our brother publication, Harvard Men’s
Health Watch, suggested that readers
give them up, at least until the folic
acid–cancer story is sorted out. And
earlier this year, results from a large
study of postmenopausal women were
published that showed multivitamin
use had little to no effect on cancer and
cardiovascular risk.
Counterarguments come from Dr.
Walter C. Willett, chair of the Harvard
School of Public Health’s nutrition department and a member of the Health
Letter’s editorial board. Dr. Willett says
the problem isn’t so much with vitamins, but the way they’ve been studied.
The randomized clinical trial, considered the gold standard in medical research, has some limitations when it
comes to long-term prevention efforts
like taking vitamins, he says. (More on
that below.) Dr. Willett also sees more
nuance, a mix of good and bad news,
than headlines allow. He’s still inclined
to give daily multivitamins the benefit of the doubt and recommends that
people take them—and look for brands
that contain lots of vitamin D.
small amounts for our bodies to function properly. That distinguishes them
from carbohydrate, fat, and protein,
which are needed in relatively large
amounts, and minerals, which aren’t
organic molecules. Thirteen vitamins
have been isolated and identified: eight
different B vitamins and vitamins A, C,
D, E, and K.
Historically, the problem with vitamins was that people didn’t get enough
of them. The vitamin-deficiency diseases have colorful names like beriberi (lack
of vitamin B1), rickets (lack of vitamin
D), and scurvy (lack of vitamin C).
But as the food supply became more
reliable and diets improved, the focus
shifted from absence to addition and
whether consuming vitamins in abundance might fend off disease and perhaps even prolong life. Test-tube and
animal experiments showed that vitamins A (in its beta carotene form), C,
and E were potent antioxidants that
could “soak up” unstable molecules capable of altering fats and proteins and
damaging DNA—the kind of damage
that eventually manifests itself as heart
disease and cancer. In several cases, the
antioxidant findings were buttressed by
results from long-term studies like the
Harvard-based Nurses’ Health Study.
Linus Pauling, the two-time Nobel
Prize winner, brought star power to
the cause with his ardent promotion
of vitamin C as a cure-all. In 1994, the
Dietary Supplement and Health Education Act (DSHEA) classified vitamins
(and herbal medicines) as dietary supplements so they didn’t need to meet
the same safety and efficacy standards
as drugs. Perhaps the demand was already there, but DSHEA took the lid
off and allowed vitamins and herbal
supplements to become a big business.
… and the bust
But amid all the vitamin mania, researchers were quietly running vitaThe boom …
Vitamins are organic (carbon-contain- mins through the gantlet of randomized
ing) compounds that we must ingest in trials. Hundreds, if not thousands,
www.health.harvard.edu
of results have now been published.
Not all the results are negative by any
means, but there’s a persuasive tilt in
that direction.
Vitamin C was first to travel from
vaunted to vanquished. Pauling’s assertion that taking large doses (500 mg or
more daily) would prevent colds was
undercut by results from several studies in the 1970s. Later, a Mayo Clinic
trial upended claims that the vitamin
could be used to treat colon cancer. Just
a few months ago, Harvard researchers
added another finding to the list that
vitamin C does little, if anything, to
prevent heart attacks and strokes.
Vitamin E looked promising because
of its strong antioxidant effects—and
doctors believed it, too: a 1999 survey
found that almost 40% of cardiologists
took vitamin E. But randomized trial results haven’t been kind to E, either, and
2005 was a particularly rough year. Alzheimer’s disease, heart disease, cancer
—reports that year made the vitamin
out as ineffectual against all three.
And it’s been a bumpy ride for the
B vitamins, too. The hope was that a
trio of them—B6, B12, and folic acid—
might be an easy way to rake back heart
disease risk because they lower levels
of homocysteine, an amino acid in the
blood. In randomized trials, they’ve
reduced homocysteine levels, but that
reduction hasn’t translated into lower
heart disease risk. An exception to the
gloom: a major meta-analysis several
years ago found that folic acid supplements do reduce the risk of stroke.
What doctors do
The Health Letter editorial board is split on multivitamins. Dr. Walter C. Willett takes them and
says we should too, as a precaution against poor
nutrition and as a way to boost our vitamin D
intake. The newsletter’s other nutrition expert,
Dr. Bruce Bistrian, doesn’t and depends on a
good diet and lots of fish (five servings a week)
to protect his health, although he believes others might benefit from multivitamins.
When we surveyed the other doctors on our editorial board, it was close: eight takers,
seven nontakers. One doctor said he took them occasionally. Another is in a blinded
study, and he doesn’t know if the pill he is taking is the multivitamin or the placebo.
The multivitamin takers said they took them for the vitamin D content and as an insurance against the holes in their diets. Most of the nontakers said taking multivitamins
was unnecessary because they eat a healthful diet with enough fruit and vegetables.
or the control (classically, a placebo
pill). Random assignment means letting chance decide which group each
person goes into. After a prescribed
period of time, researchers look for differences between the intervention and
control groups. The power of these trials
comes from the fact that randomization
—if done carefully—works to make
comparison groups alike, so the only
explanation for a difference in outcome
is the effect of an intervention.
But when it comes to evaluating
how well vitamins—and other preventive measures—protect us against
chronic diseases like cancer and heart
disease, the randomized trial may have
some blind spots. For one thing, it may
take decades for conditions like cancer
or dementia to develop. So even if a
trial lasts many years, that might not
be long enough to pick up on the effect of an inter vention, particularly if
Limits of randomized trials
it’s subtle. In the Harvard-based PhysiMuch of this bad news for vitamins has cians’ Health Study, beta carotene had
come in the form of negative results no effect on cognitive function after
from randomized trials, which in medi- 12 years, but six years later, some modcal circles is damning evidence indeed. est benefit seemed to have kicked in.
The randomized trial is considered the
There’s also a question about applytrue test in medicine—the final arbiter ing narrow randomized trial results to
of whether or not something works.
everyone. Strictly speaking, the results
In simplified terms, a randomized of any trial are applicable only to the
trial involves enrolling a group of peo- sorts of people included in the trial, so
ple into a study and randomly assigning the negative result from, say, a trial of
them to receive either the intervention older men who took a vitamin for five
under investigation (vitamins in this years are relevant only to older men,
context, but it can be almost anything) not to the population as a whole. Ranwww.health.harvard.edu
domized trials give answers for slices of
the pie, not the entire thing.
Results from randomized trials can
also be misleading if the findings for a
subset of people differ from the overall
ones. For example, in 2005, the highprofile Women’s Health Study dealt
another setback to vitamin E when it
showed no cardiovascular benefits from
taking the vitamin. But when the researchers analyzed women ages 65 and
older separately, they found that taking the vitamin was associated with a
26% reduction in cardiovascular events.
Subgroup analyses can be abused by researchers “data dredging” for provocative results, but they can also show that
trial results aren’t uniform.
That elusive bottom line
Despite all the back-and-forth, there are
a couple of areas of agreement. Added
vitamins have lost their sheen, and there
are more doubts than ever about taking
them in pill form. Large doses of single
vitamins aren’t a good idea: the benefit
is doubtful, and some can cause harm.
The notable exceptions are vitamin D,
and folic acid for young women.
And what about multivitamins?
The doses they contain aren’t likely to
pose any risk, but the leap of faith that
we’re getting benefit from them has
definitely gotten longer. On the other
hand, it’s a reasonable choice to take a
multivitamin—or not to, if you have a
well-rounded diet.
April 2009
Harvard Health Letter |
7
B Y T H E W A Y, D O C T O R
with Anthony L. Komaroff, M.D., Editor in Chief
Q
I’m 65, and I don’t think my memory is as
good as it once was. I read about a study that
says you can improve your memory by eating
less. Is there any truth to it? It sounds too good
to be true.
Can cutting
calories help
my memory?
A
Should I be
concerned
about omega-3
fats and
bleeding?
Q
It’s not as crazy as it might sound.
The study you’re referring to was published
in the prestigious Proceedings of the National Academy of Sciences (PNAS), and it came after literally
thousands of other studies of calorie restriction. In
all animals that have been studied, from the simplest creatures to complicated mammals like us,
cutting daily calorie consumption by about 30%
improves vitality and lengthens life.
In the PNAS study, 50 people whose average
age was about 60 were randomly assigned to one
of three diets: one that reduced daily calorie intake
by 30%; another that included a large amount of
unsaturated fat (the type of fat found in plantbased oils like olive oil and in fish), an eating pattern that some studies suggest might be a memory
booster; and a third that involved people just
following their usual diets.
All the people in the study scored similarly on a
memory test when the three-month study started.
But at its conclusion, the study volunteers assigned
to the restricted-calorie diet had scores on the test
that were 20% better than at the beginning of the
study, while those in the other two groups showed
no improvement. The improved memory scores
correlated with metabolic changes (decreases in
levels of insulin and C-reactive protein, an inflammatory marker) that might strengthen the connections among the brain cells that are responsible for
memory.
This was a small, relatively short study, so it’s not
even close to being definitive. And even if larger
and longer studies were to confirm the results, it’s
fair to ask about the practical application. How
many of us could manage a diet that cut our calories back by 30%? However, scientists are working
on drugs that mimic the effects of calorie restriction, and those drugs already have shown benefits
in mice—although the impact on memory has yet
to be evaluated.
In my view, severe calorie restriction isn’t likely
to be realistic for most people, although I know
some who have adopted it and are sticking with it.
But I think it is possible that someday there will be
medications that help with memory loss and many
other problems associated with aging.
I’ve been taking omega-3 fats and have two day out. That’s a lot of fish, and it would be expenbig bruises. Even small doses of aspirin sive. The AHA seems to acknowledge this problem
cause me to bruise. My doctor is not concerned, by making fish oil capsules an option.
but should I be?
I don’t think the average person taking two,
even three, grams of fish oil a day should have any
Most people take omega-3 fats in the form problem with bleeding. But with your tendency to
of fish oil. While the evidence isn’t airtight, bruise easily, it seems like you’re probably not in
I think fish oil is good for the heart. In fact, like the average-person category. Bruises are collecyou, I take it myself—and we have plenty of tions of blood under the skin, and bruising easily
company.
is a sign of a tendency to bleed. I think you should
The American Heart Association (AHA) rec- talk to your doctor about possibly seeing a specialommends that people with documented coro- ist who can investigate your problem.
nary artery disease—a narrowing of the arteries
that supply the heart—get about a gram of the
omega-3s found in fish a day, preferably by eating
fish. It’s possible to eat that way: a 3-ounce serving
of wild coho salmon contains roughly that amount
of omega-3s. But you’d have to eat fish day in and
A
Send us a
question
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8 | Harvard Health Letter
April 2009
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