Vitamins
& Minerals
"Vitamin trouble," Stuart replied. "She took vitamin
D when she needed A. She took vitamin B when she was short of C, and
her system became overloaded with riboflavin, thiamine hydrochloride,
and pyridoxine, the need for which in human nutrition has not yet
been established." --From Stuart Little, by E.B. White (1945)
Dietary Insurance: A Daily
Multivitamin
If you eat a healthy diet, do you need to take vitamins? Not long
ago, the answer from most experts would have been a resounding "no".
Today, though, there's good evidence that taking a daily multivitamin
makes sense for most adults.
What's changed? Not only have scientists determined why we need pyridoxine
(vitamin B6), but they are also accumulating evidence that this vitamin
and others do much more than ward off the so-called diseases of deficiency,
things like scurvy and rickets. Intake of several vitamins above the
minimum daily requirement may prevent heart disease, cancer, osteoporosis,
and other chromic diseases.
This summary will focus on vitamins with newly recognized or suspected
roles in health and disease. It will present some of the evidence
about vitamins' possible new roles, point out how to get more of these
in your diet, and assess the value of taking a daily multivitamin.
Vitamin A:
Vitamin A does much more than help you see in the dark. It stimulates
the production and activity of white blood cells, takes part in remodeling
bone, helps maintain the health of endothelial cells (those lining
the body's interior surfaces), and regulates cell growth and division.
This latter role had researchers exploring for years whether insufficient
vitamin A caused cancer. Several studies have dashed this hypothesis,
as have randomized trials of supplements containing beta carotene,
a precursor of vitamin A.
Although it's relatively easy to get too little vitamin A, it's also
easy to get too much. Intake of up to 10,000 IU, twice the current
recommended daily level, is thought to be safe. However, there is
some evidence that this much preformed vitamin A might increase the
risk of hip fracture or some birth defects.
Optimal Intake: The current recommended intake of
vitamin A is 5,000 IU for men and 4,000 IU for women. Many breakfast
cereals, juices, dairy products, and other foods are fortified with
vitamin A. Many fruits and vegetables, and some supplements, also
contain beta-carotene and other vitamin A precursors, which the body
can turn into vitamin A. In contrast to preformed vitamin A, beta-carotene
is not toxic even at high levels of intake. The body can form vitamin
A from beta-carotene as needed, and there is no need to monitor intake
levels, as there is with preformed vitamin A. Therefore, it is preferable
to choose a vitamin supplement that has all or the vast majority of
its vitamin A in the form of beta-carotene. Another reason to avoid
too much preformed vitamin A is that it may interfere with the beneficial
actions of vitamin D.
The 3 Bs: Vitamin B6, Vitamin
B12, and Folic Acid
One of the advances that changed the way we look at vitamins was the
discovery that too little folic acid, one of the eight B vitamins,
is linked to birth defects such as spina bifida and anencephaly. Fifty
years ago, no one knew what caused these birth defects, which occur
when the early development of tissues that eventually become the spinal
cord, the tissues that surround it, or the brain goes awry. Twenty
five years ago, British researchers found that mothers of children
with spina bifida had low vitamin levels. Eventually, two large trials
in which women were randomly assigned to take folic acid or a placebo
showed that getting too little folic acid increased a woman's chances
of having a baby with spina bifida or anencephaly and that getting
enough folic acid could prevent these birth defects.
Enough folic acid, at least 400 micrograms a day, isn't always easy
to get from food. That's why women of childbearing age are urged to
take extra folic acid. It's also why the US Food and Drug Administration
now requires that folic acid be added to most enriched breads, flour,
cornmeal, pastas, rice, and other grain products, along with the iron
and other micronutrients that have been added for years.
The other exciting discovery about folic acid and two other B vitamins
is that they may help fight heart disease and some types of cancer.
It's too early to tell if there's merely an association between increased
intake of folic acid and other B vitamins and heart disease or cancer,
or if high intakes prevent these chronic diseases.
B Vitamins and Heart Disease
In 1968, a Boston pathologist investigaed the deaths of two children
from massive strokes. Both had inherited conditions that caused them
to have high levels of a protein breakdown product called homocysteine
in their blood, and both had arteries as clogged with cholesterol
as those of a 65-year-old fast food addict. Putting one and one together,
he hypothesized that high levels of homocysteine contribute to the
artery-clogging process of atherosclerosis. Since then, some-but not
all-studies have linked high levels of this breakdown product, called
homocysteine, with increased risks of heart disease and stroke.
Folic acid, vitamin B6, and vitamin B12 play key roles in recycling
homocysteine into methionine, one of the 20 or so building blocks
from which the body builds new proteins. Without enough folic acid,
vitamin B6, and vitamin B12, this recycling process becomes inefficient
and homocysteine levels increase. Several observational studies show
that high levels of homocysteine are associated with increased risks
of heart disease and stroke. Increasing intake of folic acid, vitamin
B6, and vitamin B12 decreases homocysteine levels. And some observational
studies show lower risks of cardiovascular disease among people with
higher intakes of folic acid, those who use multivitamin supplements,
or those with higher levels of serum folate (the form of folic acid
found in the body). However, other prospective studies show little
or no association between homocysteine and cardiovascular disease.
The first large trial of homocysteine to be completed ended with negative
results. In the Vitamin Intervention for Stroke Prevention trial,
3680 adults who had had nondisabling strokes took a pill containing
high doses of vitamins B6, B12, and folic acid or one containing low
doses of these three B vitamins. After two years, second strokes,
heart attacks and other coronary heart disease events, and deaths
were the same in the two groups. However, in that trial, high levels
of homocysteine at baseline were associated with higher risk of cardiovascular
disease. Other ongoing randomized trials, such as the Women's Antioxidant
Cardiovascular Study and the Vitamin Intervention in Stroke Prevention
Study should yield more definitive answers regarding homocysteine,
B vitamins, and cardiovascular risk.
Folic Acid and Cancer
In addition to recycling homocysteine, folate plays a key role in
building DNA, the complex compound that forms our genetic blueprint.
Observational studies show that people who get higher than average
amounts of folic acid from their diets or supplements have lower risks
of colon cancer and breast cancer. This could be especially important
for those who drink alcohol, since alcohol blocks the absorption of
folic acid and inactivates circulating folate. An interesting observation
from the Nurses' Health Study is that high intake of folic acid blunts
the increased risk of breast cancer seen among women who have more
than one alcoholic drink a day.
Optimal Intake: The definition of a healthy daily
intake of B vitamins isn't set in stone, and is likely to change over
the next few years as data from ongoing randomized trials are evaluated.
Because only a fraction of U.S. adults currently get the recommended
daily intake of B vitamins by diet alone, use of a multivitamin supplement
will become increasingly important.
Folic Acid: The current recommended intake for folic
acid is 400 micrograms per day. There are many excellent sources of
folic acid, including prepared breakfast cereals, beans, and fortified
grains.
Vitamin B6: A healthy diet should include 1.3 to
1.7 milligrams of vitamin B6. Higher doses have been tested as a treatment
for conditions ranging from premenstrual syndrome to attention deficit
disorder and carpal tunnel syndrome. To date, there is little evidence
that it works.
Vitamin B12: The current recommended intake for vitamin
B12 is 6 micrograms per day. Vitamin B12 deficiency can be caused
by pernicious anemia, due to a lack of "intrinsic factor"
(a substance secreted by gastric cells that binds to vitamin B12 and
enables its absorption). A more common cause of deficiency is often
diagnosed in older people who have difficulty absorbing vitamin B12
from unfortified foods; such people can typically absorb vitamin B12
from fortified foods or supplements, however, providing yet another
reason to take a multivitamin. Symptoms of B12 deficiency include
memory loss, disorientation, hallucinations, and tingling in the arms
and legs. Some people diagnosed with dementia or Alzheimer's disease
are actually suffering from the more reversible vitamin B12 deficiency.
Vitamin C: Vitamin C has been in the public eye for
a long time. Even before its discovery in 1932, nutrition experts
recognized that something in citrus fruits could prevent scurvy, a
disease that killed as many as 2 million sailors between 1500 and
1800. More recently, Nobel laureate Linus Pauling promoted daily megadoses
of vitamin C (the amount in 12 to 24 oranges) as a way to prevent
colds and protect the body from other chronic diseases.
There's no question that vitamin C plays a role in controlling infections.
It's also a powerful antioxidant that can neutralize harmful free
radicals, and it helps make collagen, a tissue needed for healthy
bones, teeth, gums, and blood vessels. The question is, do you need
lots of vitamin C to keep you healthy?
No. Vitamin C's cold-fighting potential certainly hasn't panned out.
Small trials suggest that the amount of vitamin C in a typical multivitamin
taken at the start of a cold might ease symptoms, but there's no evidence
that megadoses make a difference, or that they prevent colds. Studies
of vitamin C and heart disease, cancer, and eye diseases such as cataract
and macular degeneration also show no clear patterns.
Optimal Intake: The current recommended dietary intake
for vitamin C is 90 mg for men and 75 mg for women (add an extra 35
mg for smokers). There's no good evidence that megadoses of vitamin
C improve health. As the evidence continues to unfold, 200 to 300
mg of vitamin C a day appears to be a good target. This is easy to
hit with a good diet and a standard multivitamin. Excellent food sources
of vitamin C are citrus fruits or citrus juices, berries, green and
red peppers, tomatoes, broccoli, and spinach. Many breakfast cereals
are also fortified with vitamin C.
Vitamin D: If you live north of the line connecting
San Francisco to Philadelphia, odds are you don't get enough vitamin
D. The same holds true if you don't, or can't, get outside for at
least a 15-minute daily walk in the sun. African-Americans and others
with dark skin tend to have much lower levels of vitamin D, due to
less formation of the vitamin from the action of sunlight on skin.
A study of people admitted to a Boston hospital, for example, showed
that 57% were deficient in vitamin D.
Vitamin D helps ensure that the body absorbs and retains calcium and
phosphorus, both critical for building bone. Laboratory studies also
show that vitamin D keeps cancer cells from growing and dividing.
Some preliminary studies indicate that insufficient intake of vitamin
D is associated with an increased risk of fractures, and that vitamin
D supplementation may prevent them. It may also help prevent falls,
a common problem that leads to substantial disability and death in
older people. Other early studies suggest an association between low
vitamin D intake and increased risks of prostate, breast, colon, and
other cancers.
Optimal Intake: The current recommended intake of
vitamin D is 5 micrograms up to age 50, 10 micrograms between the
ages of 51 and 70, and 15 micrograms after age 70. Optimal intakes
are higher, though, with 25 micrograms (1000 IU) recommended for those
over age 2. Very few foods naturally contain vitamin D. Good sources
include dairy products and breakfast cereals (which are fortified
with vitamin D), and fatty fish such as salmon and tuna. For most
people, the best way to get the recommended daily intake is by taking
a multivitamin, but the level in most multivitamins (10 micrograms)
is too low.
Vitamin E: For a time, vitamin E supplements looked
like an easy way to prevent heart disease. Promising observational
studies, including the Nurses' Health Study and Health Professionals
Follow-up Study, suggested 20% to 40% reductions in coronary heart
disease risk among individuals who took vitamin E supplements (usually
containing 400 IU or more) for least two years.
The results of several randomized trials have dampened enthusiasm
for vitamin E's ability to prevent heart attacks or deaths from heart
disease among individuals with heart disease or those at high risk
for it. In the GISSI Prevention Trial, the results were mixed but
mostly showed no preventive effects after more than three years of
treatment with vitamin E among 11,000 heart attack survivors. Results
from the Heart Outcomes Prevention Evaluation (HOPE) trial also showed
no benefit of four years worth of vitamin E supplementation among
more than 9,500 men and women already diagnosed with heart disease
or at high risk for it. Based on these and other studies, the American
Heart Association has concluded that "the scientific data do
not justify the use of antioxidant vitamin supplements [such as vitamin
E] for CVD risk reduction."
A recent scientific analysis raised questions about whether high doses
of vitamin E supplements might increase the risk of dying. The authors
gathered and re-analyzed data from 19 clinical trials of vitamin E,
including the GISSI and HOPE studies; they found a higher rate of
death in trials where patients consumed more than 400 IU of supplements
per day. While this meta-analysis drew headlines when it was released
online in November 2004, there are limitations to the conclusions
that can be drawn from it. Some of the findings are based on very
small studies; furthermore, many of the high-dose trials of Vitamin
E included in the analysis were done on people who had chronic diseases,
such as heart disease or Alzheimer's disease. So it is not clear that
these findings would apply to healthy people.
It's entirely possible that in secondary prevention trials, the use
of drugs such as aspirin, beta blockers, and ACE inhibitors mask a
modest effect of vitamin E, and that it may have benefits among healthier
people. Ongoing randomized trials of vitamin E, such as the Women's
Health Study and SU.VI.MAX will tell us more about its possible benefits
in the coming years.
Optimal Intake: The recommended daily intake of
vitamin E from food now stands at 15 milligrams from food. That's
the equivalent of 22 IU from natural-source vitamin E or 33 IUs of
the synthetic form. Researchers are still writing the book on vitamin
E. Some small studies have suggested that vitamin E supplements might
interfere with statins, but this hypothesis was refuted in a large
trial. While the data are sparse and conflicting, evidence from some
observational studies suggests that at least 400 IU of vitamin E per
day, and possibly more, are needed for optimal health. Since standard
multivitamins usually contain around 30 IU, a separate vitamin E supplement
is needed to achieve this level. Current guidelines say that consuming
more than 1000 mg of supplemental vitamin E per day is not considered
safe; that's the equivalent of a supplement with 1,500 IU of natural-source
vitamin E or 1,100 IU of synthetic vitamin E.
Vitamin K: Vitamin K helps make six of the 13 proteins
needed for blood clotting. Its role in maintaining the clotting cascade
is so important that people who take anticoagulants such as warfarin
(Coumadin) must be careful to keep their vitamin K intake stable.
Lately, researchers have demonstrated that vitamin K is also involved
in building bone. Low levels of circulating vitamin K have been linked
with low bone density, and supplementation with vitamin K shows improvements
in biochemical measures of bone health. A report from the Nurses'
Health Study suggests that women who get at least 110 micrograms of
vitamin K a day are 30% less likely to break a hip as women who get
less than that. Among the nurses, eating a serving of lettuce or other
green leafy vegetable a day cut the risk of hip fracture in half when
compared with eating one serving a week. Data from the Framingham
Heart Study also shows an association between high vitamin K intake
and reduced risk of hip fracture.
Optimal Intake: The recommended daily intake for
vitamin K is 80 micrograms for men and 65 for women. Because this
vitamin is found in so many foods, especially green leafy vegetables
and commonly used cooking oils, most adults get enough of it. According
to a 1996 survey, though, a substantial number of Americans, particularly
children and young adults, aren't getting the vitamin K they need.
Antioxidants
Our cells must constantly contend with nasty substances called free
radicals. They can damage DNA, the inside or artery walls, proteins
in the eye--just about any substance or tissue imaginable. Some free
radicals are made inside the body, inevitable byproducts of turning
food into energy. Others come from the air we breathe and the food
we eat.
We aren't defenseless against free radicals. We extract free-radical
fighters, called antioxidants, from food. Fruits, vegetables, and
other plant-based foods deliver dozens, if not hundreds, of antioxidants.
The most common are vitamin C, vitamin E, beta-carotene and related
carotenoids. Food also supplies minerals such as selenium and manganese,
which are needed by enzymes that destroy free radicals.
During the 1990s, the term antioxidants became a huge nutritional
buzz word. Antioxidants were promoted as wonder agents that could
prevent heart disease, cancer, cataracts, memory loss, and a host
of other conditions.
It's true that the package of antioxidants, minerals, fiber, and other
substances found in fruits, vegetables, and whole grains help prevent
a variety of chronic diseases. Whether high doses vitamin C, vitamin
E, or other antioxidants can accomplish the same feat is an open question.
The evidence accumulated so far isn't promising. Randomized trials
of vitamin C, vitamin E, and beta-carotene haven't revealed much in
the way of protection from heart disease, cancer, or aging-related
eye diseases. Ongoing trials of other antioxidants, such as lutein
and zeaxanthin for macular degeneration and lycopene for prostate
cancer, are underway.
The Bottom Line
A standard multivitamin supplement doesn't come close to making up
for an unhealthy diet. It provides a dozen or so of the vitamins known
to maintain health, a mere shadow of what's available from eating
plenty of fruits, vegetables, and whole grains. Instead, a daily multivitamin
provides a sort of nutritional safety net.
While most people get enough vitamins to avoid the classic deficiency
diseases, relatively few get enough of five key vitamins that may
be important in preventing several chronic diseases. These include:
• Folic acid
• Vitamin B6
• Vitamin B12
• Vitamin D
• Vitamin E
A standard, store-brand, RDA-level multivitamin can supply you with
enough of these vitamins for under $40 a year. It's about the least
expensive insurance you can buy.
By Harvard School of Public Health
