Vitamin deficiency syndromes such as scurvy and beriberi are uncommon
in Western societies. However, suboptimal intake of some vitamins, above levels
causing classic vitamin deficiency, is a risk factor for chronic diseases
and common in the general population, especially the elderly. Suboptimal folic
acid levels, along with suboptimal levels of vitamins B6 and B12, are a risk factor for cardiovascular disease, neural tube defects,
and colon and breast cancer; low levels of vitamin D contribute to osteopenia
and fractures; and low levels of the antioxidant vitamins (vitamins A, E,
and C) may increase risk for several chronic diseases. Most people do not
consume an optimal amount of all vitamins by diet alone. Pending strong evidence
of effectiveness from randomized trials, it appears prudent for all adults
to take vitamin supplements. The evidence base for tailoring the contents
of multivitamins to specific characteristics of patients such as age, sex,
and physical activity and for testing vitamin levels to guide specific supplementation
practices is limited. Physicians should make specific efforts to learn about
their patients' use of vitamins to ensure that they are taking vitamins they
should, such as folate supplementation for women in the childbearing years,
and avoiding dangerous practices such as high doses of vitamin A during pregnancy
or massive doses of fat-soluble vitamins at any age.
In the absence of specific predisposing conditions, a usual North American
diet is sufficient to prevent overt vitamin deficiency diseases such as scurvy,
pellagra, and beriberi. However, insufficient vitamin intake is apparently
a cause of chronic diseases. Recent evidence has shown that suboptimal levels
of vitamins, even well above those causing deficiency syndromes, are risk
factors for chronic diseases such as cardiovascular disease, cancer, and osteoporosis.
A large proportion of the general population is apparently at increased risk
for this reason.
Suboptimal Amounts of Vitamins
Suboptimal levels of a vitamin can be defined as those associated with
abnormalities of metabolism that can be corrected by supplementation with
that vitamin. For example, many people in the general population have serum
homocysteine levels from 1.62 to 2.03 mg/L (12-15 µmol/L),1
which fall to baseline levels of 1.08 to 1.35 mg/L (8-10 µmol/L) after
a few weeks of supplementation with folate, along with vitamins B12
and B6.2 Similarly, in many elderly
people, methylmalonic acid levels fall with vitamin B12 supplementation,2 and elevated levels of parathyroid hormone fall with
vitamin D supplementation.3 Measurements of
vitamin levels in blood, serum, or red blood cells, at least with current
reference points for abnormality, are not a reliable guide to this form of
deficiency; in one study,2 supplementation
substantially reduced serum homocysteine levels in elderly patients with normal
serum folate concentrations.
For some vitamins, the concept of suboptimal levels is also supported
by randomized trial evidence that supplementation reduces the rate of clinical
events. The research evidence is conclusive that folate during the first trimester
of pregnancy reduces the risk of neural tube defects in women at increased
risk.4 Similarly, vitamin D supplementation,
along with calcium, reduces the risk of fractures in elderly women with osteoporosis.5
The high prevalence of suboptimal vitamin levels implies that the usual
US diet provides an insufficient amount of these vitamins. Fruits and vegetables
are the main dietary source of many vitamins, and health experts have long
recommended at least 5 daily servings. A recent survey showed that only 20%
to 30% of the population actually meet this goal.6
Although vitamin D is added to milk, many people (especially the elderly)
do not consume enough dairy products to get a sufficient amount of vitamin
D.3,7,8 Folate supplementation
of cereal products is sufficient to raise folate intake only by about 100
µg, so many people do not meet the goal of 400 µg/d.9
Food preparation may decrease the activity for some vitamins; for example,
keeping food hot longer than 2 hours results in a more than 10% loss of vitamin
C, folate, and vitamin B6.10 Vitamins
are also lost during chilling, storage, and reheating, including more than
30% of vitamin C and folate.10 Alcohol consumption
increases folate requirements,11 and aging
is associated with decreased absorption of some vitamins such as B12.
Correcting Suboptimal Vitamin Levels
Three options exist for correcting suboptimal vitamin intake. First,
physicians could counsel patients to improve their diet. This approach would
be relatively inefficient if the only goal were to increase vitamin consumption
because patients would have to be counseled individually, and it is difficult
to get individual patients to change their diets. Nevertheless, dietary change
is a central component of an overall program of preventive care.12
Foods contain thousands of compounds that may be biologically active, including
hundreds of natural antioxidants, carotenoids, and flavonoids. For these reasons,
vitamin supplementation is not an adequate substitute for a good diet.
A second option is to add vitamins to generally consumed foods. The
United States has been adding vitamin D to milk and some other dairy products
since the 1930s because of the high prevalence of rickets and osteomalacia
in northern climates at that time. Beginning in 1996, folate has been added
to cereals to reduce the rate of neural tube defects. However, this approach
is limited by popular mistrust of adding chemicals to food.
A third option is for individuals to take vitamin supplements. All major
pharmacies carry their own brands of multivitamins as well as a variety of
other brand name and generic multivitamins. The contents of basic multivitamins
are remarkably similar across brands, with each having at least 100% of the
daily value for nearly all vitamins (with the exception of vitamin K). In
addition to vitamins, so-called multivitamins often contain other food supplements
such as minerals and herbs. The amount of calcium in multivitamins is typically
between 40 and 160 mg, well below the generally recommended dose of 1000 to
1500 mg/d,13 so one cannot depend on multivitamins
for meeting calcium needs. Most multivitamins contain iron, whose supplementation
may not be advisable for men and nonmenstruating women, given the high prevalence
of the gene for hemochromatosis.
The cost for brand-name multivitamins may be around $20 to $30 annually,
and some special formulations may cost a great deal more. However, one can
easily buy large quantities (eg, 250-500 pills) of generic multivitamins for
around $10 annually. We are aware of no evidence that the various multivitamins
differ in bioavailability because of the way they are formulated. Patients
can buy individual vitamins at an even lower price, which may make sense for
women in the childbearing years, for whom folate supplementation might cost
only $5 to $10 annually.
Special multivitamins are sold for subgroups of the population such
as active men, perimenopausal women, and the elderly. The Internet and health-food
stores are filled with promotions for these special-purpose multivitamins,
which are often costly. The only evidence-based arguments for taking more
than a common multivitamin once a day pertain to the elderly and women who
might become pregnant. The recommended intake for vitamins B12
and D in the elderly is closer to 2 times the dietary reference intake. For
women who might become pregnant, folate at 800 µg/d is appropriate.
Some vitamins, such as thiamin, riboflavin, and niacin, have received
little mention in this review. Although by definition severe deficiency of
these vitamins is associated with disease, they have so far not been associated
with chronic diseases. The absence of evidence that these vitamins are associated
with chronic diseases might be because those associations do not exist, ordinary
diets provide sufficient amounts to prevent chronic disease, or the research
has not yet been done to discover these relationships.
Tests for vitamin levels in blood, serum, or red blood cells are now
offered by commercial laboratories, as are tests for substances such as homocysteine
that mark abnormal vitamin-related metabolism.14
The availability of these tests raises these questions: Would this additional
information lead to better preventive or therapeutic interventions than might
be offered without the test? If so, what kind of patients would benefit?
It is certainly possible that some individuals, because of their diets
or genetic polymorphisms, have unusual vitamin needs. Many of these people
can be detected by a simple review of their medical problems, including alcoholism.
The MTHFR polymorphism, which is associated with
low folate levels and perhaps increased rates of cardiovascular disease, is
the best studied. The abnormal MTHFR gene occurs
in 5% to 15% of the population15 and might
have effects on diseases related to folate deficiency. The MTHFR gene would be detected only by specific testing not yet commercially
available. However, research into the metabolic and clinical effects of these
disorders is in its infancy and not strong enough to confidently guide tailored
supplementation programs. Therefore, we believe that testing individuals who
do not have a well-recognized indication is premature.
We recommend that all adults take one multivitamin daily. This practice
is justified mainly by the known and suspected benefits of supplemental folate
and vitamins B12, B6, and D in preventing cardiovascular
disease, cancer, and osteoporosis and because multivitamins at that dose are
safe and inexpensive.16 It is reasonable to
consider a dose of 2 ordinary multivitamins daily in the elderly, specifically
because of the high prevalence of suboptimal vitamin B12 and D
intake. However, it might be safer to supplement 1 multivitamin with additional
vitamins B12 and D, taken separately, given the possibility that
increased vitamin A intake might increase the risk of hip fracture17 and that the iron in most multivitamins may increase
the risk of hemochromatosis in some people. The increased folate requirement
in people with high alcohol intake can be met with 1 multivitamin daily or
folic acid supplementation alone. For women attempting to conceive, a multivitamin
plus folate at 400 µg/d is appropriate, given evidence of additional
benefit with higher folate levels.18 We recommend
multivitamins, rather than individual vitamins, because multivitamins are
simpler to take and cheaper than the individual vitamins taken separately
and because a large proportion of the population needs supplements of more
than one vitamin.
Physicians often do not ask about vitamin use. Patients may not volunteer
information about their vitamin use, fearing that the physician would disapprove
of unconventional use of vitamins. Therefore, physicians should specifically
ask about vitamin use with 2 goals in mind. First, they should be sure that
patients know about the vitamin supplements they clearly should be taking,
such as folate during the childbearing years. Second, physicians should be
sure the patient is not taking vitamins in harmful doses, such as very large
doses of vitamin D or even moderate doses of vitamin A during the first trimester
of pregnancy. Within these rather broad limits, we believe that physicians
should be interested and not directive, even when it seems the patient has
unfounded beliefs or apparently unhelpful practices. In this way, physicians
can avoid incurring a substantial chance of losing access to important information
about patients' vitamin use.
Additional Information About Vitamins
The evidence base for the clinical effects of vitamins is increasing
rapidly. For physicians to keep up with new developments, there is no good
alternative to electronic sources. The World Wide Web includes a vast array
of information on vitamins, most of it promotional and self-serving. Physicians
can find the most updated and credible information at the National Institutes
of Health Web site (http://www.cc.nih.gov/ccc/supplements). In
addition, Tufts University maintains an excellent nutrition Web site, as well
as a Nutrition Navigator that provides quality ratings for other nutrition
Web sites (http://www.navigator.tufts.edu). This site includes
appropriate information for patients and health care professionals. Some textbooks
and Web publications are continually updated as new research findings are
published. The Institute of Medicine has published a series of books on this
subject as well, with extensive review of the existing literature at the date
of publication.19-23
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