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 percent 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. And it’s possible that vitamin E may have potential benefits in certain subgroups of the general population: A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress.

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. But 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.

Food sources: Good sources of vitamin E include sunflower and safflower oils, oil-based salad dressings, almonds, sunflower seeds, peanut butter, and dark leafy greens.

References

1. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993; 328:1444-9.

2. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993; 328:1450-6.

3. Rimm EB, Stampfer MJ. Antioxidants for vascular disease. Med Clin North Am. 2000; 84:239-49.

4. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999; 354:447-55.

5. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342:154-60.

6. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation. 2004; 110:637-41.

7. Miller ER, 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005; 142:37-46.

8. Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005; 294:56-65.

9. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004; 164:2335-42.

10. Christen WG, Gaziano JM, Hennekens CH. Design of Physicians’ Health Study II–a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol. 2000; 10:125-34.

11. Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000.

12. Milman U, Blum S, Shapira C, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype. A prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol. 2007:ATVBAHA.107.153965.

Vitamin D

Getting vitamin D from the sun: 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. 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 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 overall mortality rates: A combined analysis of multiple studies found that taking modest levels of vitamin D supplements was associated with a statistically significant 7 percent 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 and 800 IU of vitamin D per day for an average of five 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 explore 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.)

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 to 50 micrograms (1,000 to 2,000 IU) recommended for those over age 2. If the multivitamin you take does not have 1,000 IU of 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. In fact, some people may need 3,000 or 4,000 IU per day for adequate blood levels, particularly if they have darker skin, spend winters in the northern U.S., or have little exposure to direct sunlight. If you fall into these groups, ask your physician to order a blood test for vitamin D.

Food sources: 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 1,000 IU of vitamin D to their standard multivitamin preparations.

Getting vitamin D from the sun: 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. 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.

References

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–81.

2. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004; 158:531–7.

3. Lips P, Hosking D, Lippuner K, et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006; 260:245–54.

4. Bischoff–Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson–Hughes B. Fracture prevention with vitamin D supplementation: a meta–analysis of randomized controlled trials. JAMA. 2005; 293:2257–64.

5. Boonen S, Lips P, Bouillon R, Bischoff–Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007; 92:1415–23.

6. Bischoff–Ferrari HA, Dawson–Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta–analysis. JAMA. 2004; 291:1999–2006.

7. Broe KE, Chen TC, Weinberg J, Bischoff–Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple–dose study. J Am Geriatr Soc. 2007; 55:234–9.

8. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case control study of plasma 25–hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst. 2007; 99:1120–9.

9. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25–hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296:2832–8.

10. Lappe JM, Travers–Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85:1586–91.

11. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta–analysis of randomized controlled trials. Arch Intern Med. 2007; 167:1730–7.

12. Giovannucci E. Can vitamin D reduce total mortality? Arch Intern Med. 2007; 167:1709–10.

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 two million sailors between 1500 and 1800. In 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.

References

1. Carpenter KJ. The history of scurvy and vitamin C. Cambridge: Cambridge University Press, 1986.

2. Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press, 2000.

3. Douglas RM, Hemila H, Chalker E, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2007:CD000980.

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 to 30 percent, 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 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.