Vitamins

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 specific vitamins, such as ascorbic acid (vitamin C) and cholecalciferol (vitamin D), 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 help prevent heart disease, cancer, osteoporosis, and other chromic diseases.

Much to consumers' frustration, research on vitamin supplements often finds contradictory results. This summary will cut through the confusion of conflicting findings and 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 vitamins in your diet, and it will 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 the relationship between vitamin A and cancer. Specifically, researchers looked at whether people could reduce their cancer risk by taking supplements of beta carotene, one of several precursor compounds that the body can transform into vitamin A, or by taking the active form of vitamin A (also called retinol or preformed vitamin A). Several studies and randomized trials have dashed this hypothesis.

Although it's possible to get too little vitamin A, it's easy to get too much preformed vitamin A (retinol) from supplements. Intake of up to 3,000 micrograms of preformed vitamin A, more than 3 times 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.Another reason to avoid too much preformed vitamin A is that it may interfere with the beneficial actions of vitamin D.

Optimal Intake: The current recommended intake of vitamin A is 900 micrograms of retinol for men (equivalent to 3,000 IU) and 700 micrograms of retinol for women (equivalent to 2,333 IU). Many breakfast cereals, juices, dairy products, and other foods are fortified with preformed 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 multivitamin supplement that has all or the vast majority of its vitamin A in the form of beta-carotene; many multivitamin manufacturers have already reduced the amount of preformed vitamin A in their products. Smokers should avoid high-dose single supplements of beta carotene, since some randomized trials in smokers have linked high dose supplementation with increased lung cancer risk.There is no strong reason for anyone to take separate beta-carotene supplements.

Three of the Bs: Vitamin B6, Vitamin B12, and Folate

One of the advances that changed the way we look at vitamins was the discovery that too little folate, 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. More than three decades 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 (the form of folate added to multivitamins or fortified foods) or a placebo showed that getting too little folate increased a woman's chances of having a baby with spina bifida or anencephaly and that getting enough folate could prevent these birth defects.Timing of folate is critical: For folate to be effective, it must be taken in the first few weeks after conception, often before a woman knows she is pregnant.

Enough folate, 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 as a supplement. 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.Since the advent of mandatory folate fortification in 1998, neural tube birth defects have dropped by 20-30%, and studies have shown that far fewer people have low levels of folate in their blood.

The other exciting discovery about folate and two other B vitamins, vitamin B6 and vitamin B12, 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 folate, vitamin B6, and vitamin B12 and heart disease or cancer, or if high intakes prevent these chronic diseases.

B Vitamins and Heart Disease

In 1968, a Boston pathologist investigated the deaths of two children from massive strokes. Both had inherited conditions that caused them to have extremely 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 lower, but still elevated levels of homocysteine would contribute to the artery-clogging process of atherosclerosis. Since then, most--but not all--studies have linked high levels of this breakdown product, called homocysteine, with increased risks of heart disease and stroke. However, linking higher levels of homocysteine with heart disease risk does not necessarily mean that lowering homocysteine levels will lower risk. That requires testing in randomized trials.

Folate, 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 folate, 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 folate, vitamin B6, and vitamin B12 decreases homocysteine levels. And some observational studies, including the Nurses Health Study, show lower risks of cardiovascular disease among people with higher intakes of folate, those who use multivitamin supplements, or those with higher levels of serum folate (the form of folate found in the body).

The first large trial of B vitamins to lower homocysteine and prevent heart disease and stroke ended without finding any benefit. In the Vitamin Intervention for Stroke Prevention trial, 3680 adults who had had non-disabling 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.

Similar studies in people who had a history of heart disease or were at a very high risk of heart disease--so-called "secondary prevention trials"--have had similarly discouraging results: Taking high doses of the three B vitamins lowered homocysteine levels but did not lead to a reduction in coronary heart events. But looking at heart disease as a whole may have obscured a potential benefit of at least one of the B vitamins: A recent analysis of multiple studies suggests that folic acid supplements can reduce the risk of stroke, especially in people who have not already suffered a stroke. Folic acid supplements were most protective in studies that lasted longer than 3 years or that took place in countries without folic acid fortification.

Emerging research suggests that folate may prevent heart disease through other mechanisms besides its role in homocysteine recycling. Several large randomized controlled trials of B vitamins and heart disease have yet to report results; when they do, we may have more definitive answers regarding B vitamins and cardiovascular risk in people who have a history of heart disease. But none of these studies will answer the question of whether B vitamins can protect against heart disease in healthy people. To date, no one has conducted a randomized controlled trial of folate supplementation and heart disease in healthy people, probably because it would take decades to yield results and would be very costly. Ultimately, folate supplementation may only reduce the risk of heart disease in people who have lower levels of folate intake, most likely in countries that do not fortify their food supply with folate; in people who already get enough folate in their diets, very high-doses of folate supplements may actually cause harm.

Folate 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 folate from their diets or folic acid supplements for 15 years or more 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 folate and inactivates circulating folate. An interesting observation from the Nurses' Health Study is that higher intake of folate blunts the increased risk of breast cancer seen among women who have more than one alcoholic drink a day.A more recent study from Sweden found that a high folate intake can protect against breast cancer even in women who have only a drink a day or less.

But the relationship between folate and cancer is a complicated one, especially for people at a high risk of colon cancer. Colorectal adenomas, or polyps, are pre-cancerous growths in the large intestine. A recent multiyear trial looked at whether high-dose folic acid supplements could prevent new polyps in people who had a history of polyps. The study found that taking a daily pill with 1,000 micrograms of folic acid offered no protection against new polyps, and, more worrisome, increased the risk of developing multiple or more serious polyps. Keep in mind that this study tested a very high dose of folic acid, more than two times higher than what is found in a standard multivitamin; furthermore, study participants were already at a very high risk of developing new polyps. This may be another case where timing of folate intake is critical: Getting adequate folate may prevent polyps in people who do not have them, but high dose folate supplements may speed up polyp growth in people who do.

When teasing out the relationship between any vitamin supplement and cancer, it is important to remember that cancer cells are essentially our own cells on overdrive, growing and rapidly dividing, and they have a greater need for nutrients than most of our normal cells do. Indeed, one successful chemotherapy agent works as a folate antagonist, since rapidly-dividing cells require folate to maintain their fast pace of cell division. So for people who have cancer or precancerous growths, nutritional supplements may be a double-edged sword. If you have cancer, make sure to check with your doctor before beginning any vitamin supplement regimen.

Optimal Intake: The definition of a healthy daily intake of B vitamins isn't set in stone, and it is likely to change over the next few years as data from ongoing randomized trials are evaluated. In the U.S., folic acid fortification of food has increased the percentage of adults who have adequate levels of folate in their blood. Yet only a fraction of U.S. adults currently get the recommended daily intake of all B vitamins by diet alone. So use of a multivitamin supplement will become increasingly important.

Folate: The current recommended intake for folate is 400 micrograms per day. Many foods are excellent sources of folate, including fruits and vegetables, whole grains, beans, prepared breakfast cereals, and fortified grains and grain products. People who regularly drink alcohol should make sure to get at least 600 micrograms of folate a day. It is best to achieve that level of intake through a healthy diet; taking a standard multivitamin (which contains 400 micrograms of folic acid) is added insurance. Most people should avoid taking higher doses of folate supplements.

Vitamin B6: A healthy diet should include at least 1.3 to 1.7 milligrams of vitamin B6; somewhat higher intakes than that may protect against colon cancer, but more research is needed. Good sources of vitamin B6 include fortified cereals, beans, poultry, fish, and some fruits and vegetables. Very high doses of vitamin B6 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. There's also evidence that very high doses of vitamin B6 supplements can lead to nerve damage; in light of these concerns, the Institute of Medicine set the upper limit for vitamin B6 intake in adults at 100 mg a day (an amount that can only be achieved through high dose supplements).

Vitamin B12: The current recommended intake for vitamin B12 is 2.4 micrograms per day. This vitamin is found naturally in animal products (such as fish, poultry, eggs, or dairy); it is also found in fortified breakfast cereals and enriched soy or rice milk. To avoid vitamin B12 deficiency, vegans should make sure to include B12-fortified foods or a B12 supplement in their diets. Vitamin B12 deficiency can also be caused by a lack of "intrinsic factor" (a substance secreted by gastric cells that binds to vitamin B12 and enables its absorption); this can lead to so-called "pernicious anemia," and ultimately to serious neurological damage. A much more common cause of deficiency, especially in older people, is a lack of stomach acid, because stomach acid is required to liberate vitamin B12 from food. An estimated 10 to 30 percent of adults over the age of 50 have difficulty absorbing vitamin B12 from food;(29) even people who lack adequate stomach acid 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.(30n the 1970s, Chemistry and Peace Nobel laureate Linus Pauling promoted daily megadoses of vitamin C (the amount in 12 to 24 oranges) as a way to prevent colds and some 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 for the average person, there's no evidence that megadoses make a difference, or that they prevent colds.Studies of vitamin C supplements 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 milligrams for men and 75 milligrams for women (add an extra 35 milligrams for smokers). There's no good evidence that megadoses of vitamin C improve health. As the evidence continues to unfold, 200 to 300 milligrams 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, as well as older individuals, tend to have much lower levels of vitamin D, due to less formation of the vitamin from the action of sunlight on skin. Worldwide, an estimated 1 billion people have inadequate levels of vitamin D in their blood, and deficiencies can be found in all ethnicities and age groups. A study of teens in Boston, for example, found that 42% had insufficient levels of vitamin D, while an international study of post-menopausal women with osteoporosis found that more than 60% had inadequate levels of 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, and plays a critical role in controlling infections.

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, especially when vitamin D is taken in conjunction with calcium.It may also help increase muscle strength, which in turn helps to 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 breast, colon, and other cancers,as well as increased risk of multiple sclerosis.A recent randomized trial among postmenopausal women showed significant reductions in cancer incidence among those randomized to vitamin D.

A promising report in the Archives of Internal Medicine suggests that taking vitamin D supplements may even reduce the risk of dying: A combined analysis of multiple studies found that taking modest levels of vitamin D supplements was associated with a statistically significant 7% reduction in mortality from any cause. The analysis looked at the findings from 18 randomized controlled trials that enrolled a total of nearly 60,000 study participants; most of the study participants took between 400-800 IU of vitamin D per day, for an average of 5 years. Keep in mind that this analysis has several limitations, chief among them the fact that the studies it included were not designed to explore mortality in general or specific causes of death. More research is needed before any broad claims can be made about vitamin D, chronic disease prevention, and mortality. (For more information on Vitamin D and chronic disease prevention, see Ask the Expert - Vitamin D.)

Optimal Intake: The Institute of Medicine's current recommended intake of vitamin D is 5 micrograms (200 IU) up to age 50, 10 micrograms (400 IU) between the ages of 51 and 70, and 15 micrograms (600 IU) after age 70. Optimal intakes are much higher, though, with at least 25 micrograms (1,000 IU) recommended for those over age 2. Very few foods naturally contain vitamin D. Good sources include dairy products and breakfast cereals (both of 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 supplement, but the level in most multivitamins (400 IU) is too low; encouragingly, some manufacturers have begun adding 800 or 1000 IU of vitamin D to their standard multivitamin preparations. If the multivitamin you take does not have adequate vitamin D, you may want to consider adding a separate vitamin D supplement, especially if you do not spend much time in the sun. In extremely high doses--hundreds of thousands of IU or more--vitamin D is toxic and can even cause death; but in adults, taking up to 2,000 IU per day as a supplement is safe.

Should you decide to rely on the sun to get your vitamin D, keep in mind that correctly-applied sunscreen reduces our ability to absorb vitamin D by as much as 90 percent; sunscreen takes a few minutes to have this vitamin D-dampening effect, however, so if you put it on just before you go outside, you will be able to get enough sun exposure to make some vitamin D, yet still be protected from the sun's damaging rays. In northern latitudes, however, exposure to the sun in winter will not form vitamin D (due to the angle of the sun's rays), so a supplement is advisable.

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, 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. But large randomized controlled trials of vitamin E supplementation in healthy people have yielded mixed results. In the Women's Health Study, which followed 40,000 women for 10 years, vitamin E supplements of 600 IU every other day did not significantly reduce the risk of so-called "major cardiac events" (non fatal heart attack, non-fatal stroke, or cardiovascular death); when these major cardiac events were analyzed separately, however, vitamin E supplementation was linked to a 24 percent lower risk of cardiovascular death. And among women ages 65 and older, vitamin E supplementation reduced the risk of major cardiac events by 26 percent. The SU.VI.MAX trial, meanwhile, found that seven years of low-dose vitamin E supplementation (as part of a daily antioxidant pill) reduced the risk of cancer and the risk of dying from any cause in men, but did not show these beneficial effects in women; the supplements did not offer any protection against heart disease in men or women. Over the coming years, the ongoing Physicians' Health Study II may shed more light on the potential benefits and risks of vitamin E supplementation in healthy men.

Optimal Intake: The Institute of Medicine's recommended daily intake of vitamin E from food now stands at 15 milligrams. That's the equivalent of 22 IU from natural-source vitamin E or 33 IUs of the synthetic form. Good sources of vitamin E include sunflower and safflower oils, oil-based salad dressings, almonds, sunflower seeds, peanut butter, and dark leafy greens. Researchers are still writing the book on the optimal intake of vitamin E, and the data are sparse and conflicting. For healthy people, current research suggests that a reasonable level of vitamin E intake may be about 200 IUs of synthetic vitamin E per day, an amount that is difficult to achieve from diet alone; since standard multivitamins usually contain around 30 IU, a separate vitamin E supplement is needed to achieve this level. For people who already have heart disease and are taking medications to control it, a vitamin E supplement most likely will not offer any additional benefits. Current guidelines say that consuming more than 1,000 milligrams 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 in men and women and increased bone mineral density in women.

Optimal Intake: The recommended daily intake for vitamin K is 120 micrograms for men and 90 for women. This vitamin is found in many foods, especially green leafy vegetables and commonly used cooking oils. People who do not regularly eat a lettuce salad or green leafy vegetables are likely to be deficient in their intake of vitamin K; national data suggests that only about 1 in 4 Americans meet the goal for vitamin K intake from food.(59) Some, but not all, multivitamins contain a small amount of vitamin K.

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, nuts, and whole grains. Instead, a daily multivitamin provides a sort of nutritional safety net.

W

hile 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:

• Folate (in the U.S., however, thanks to mandatory folic acid fortification of refined grains, people are less likely to be deficient)

• Vitamin B6
• • Vitamin B12
• Vitamin D

• Vitamin E (keep in mind that the jury is still out on the optimum level of vitamin E intake)

A standard, store-brand, RDA-level multivitamin can supply you with enough of these vitamins for under $40 a year; if your favorite brand of multivitamin only provides 400 IU of vitamin D, adding a separate vitamin D supplement would cost another $20. It's about the least expensive insurance you can buy.

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