The Nutrition Source – Vitamin D and Health

The Nutrition Source

Vitamin D and Health

 

Table of Contents

Low Vitamin D: A Global Concern

The Institute of Medicine’s (IOM) recommended daily intake of vitamin D is 600 IU for people ages 1 to 70, and 800 IU after age 70. (7) Yet this is overly conservative, since the best available evidence shows optimal intakes are higher, at least 800–1,000 IU for adults.

In extremely high doses—hundreds of thousands of IU or more—vitamin D is toxic and can even cause death. But in children over the age of 9 and in adults, taking up to 4,000 IU per day as a supplement is safe; ages 4 to 8, up to 3,000 IU; ages 1 to 3, 2,500 IU; ages 6 to 12 months, up to 1,500 IU; and ages 0 to 6 months, up to 1,000 IU. (7)

Many people may need 2,000 IU per day (or more) for adequate blood levels, particularly if they have darker skin, spend winters at higher latitudes (such as the northern U.S.), or spend little time in the sun. If you fall into one of these groups, which would include most of the U.S. population, taking 2,000 IU is reasonable and well within the safe range for adults. As always, it’s a good idea to discuss use of supplements with your doctor, and he or she may want to order a vitamin D blood test.

To prevent rickets, the American Academy of Pediatrics recommends vitamin D supplements of 400 IU per day for breastfed infants, and also for non-breastfed infants and children who do not drink at least a liter of vitamin D fortified milk each day. (6)  Infants and children at high risk of deficiency—those who are born premature, have dark skin, or live at high latitudes—may need supplements of up to 800 IU per day, especially in the winter.

If you live north of the line connecting San Francisco to Philadelphia and Athens to Beijing, odds are that you don’t get enough vitamin D. The same holds true if you don’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, as do people who are overweight or obese.

Worldwide, inadequate vitamin D is common, and deficiencies can be found on all continents, in all ethnic groups, and across all ages. Some surveys suggest that perhaps half of the world’s population has inadequate blood levels of vitamin D. (13)  Indeed, in industrialized countries, doctors are even seeing the resurgence of rickets, the bone-weakening disease that had been largely eradicated through vitamin D fortification. (46)

Why are these widespread low levels of vitamin D such a great concern? Because research conducted over the past decade suggests that vitamin D plays a much broader disease-fighting role than once thought.

Being “D-ficient” may increase the risk of a host of chronic diseases, such as osteoporosis, heart disease, some cancers, and multiple sclerosis, as well as infectious diseases, such as tuberculosis and even the seasonal flu.

Currently, there’s scientific debate about how much vitamin D people need each day. The Institute of Medicine (IOM), in a long-awaited report released in November 2010 recommends increasing the daily vitamin D intake for children and adults in the U.S. and Canada, to 600 IU per day for people ages 1 to 70, and 800 IU for people over age 70. (7) The report also recognized the safety of vitamin D by increasing the upper limit from 2,000 to 4,000 IU per day, and acknowledged that even at 4,000 IU per day, there was no good evidence of harm.

The new guidelines, however, are overly conservative about the recommended intake, and they do not give enough weight to some of the latest science on vitamin D and health. For bone health and chronic disease prevention, many people are likely to need more vitamin D than even these new government guidelines recommend.

 

Vitamin D Sources and Function

Vitamin D is both a nutrient we eat and a hormone our bodies make. Few foods are naturally rich in vitamin D, so the biggest dietary sources of vitamin D are fortified foods and vitamin supplements.

VITAMIN D FROM FOOD AND SUPLEMENTS

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 enough vitamin D is 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. If the multivitamin you take does not have 800 or 1,000 IU of vitamin D, you may want to consider adding a separate vitamin D supplement, especially if you don’t spend much time in the sun. Talk to your healthcare provider.

The body also manufactures vitamin D from cholesterol, through a process triggered by the action of sunlight on skin, hence its nickname, “the sunshine vitamin.”  Yet many people do not make enough vitamin D from the sun, among them, people who have a darker skin tone, who are overweight, who are older, and who cover up when they are in the sun. (1)

Correctly applied sunscreen reduces our ability to absorb vitamin D by more than 90 percent. (8) And not all sunlight is created equal: The sun’s ultraviolet B (UVB) rays—the so-called “tanning” rays, and the rays that trigger the skin to produce vitamin D—are stronger near the equator and weaker at higher latitudes. So in the fall and winter, people who live at higher latitudes (in the northern U.S. and Europe, for example) can’t make much if any vitamin D from the sun. (8)

 

Read more: what may increase your risk for low vitamin D

Vitamin D helps ensure that the body absorbs and retains calcium and phosphorus, both critical for building bone. Laboratory studies show that vitamin D can reduce cancer cell growth, can increase muscle strength and reduce falls in older people, and plays a critical role in controlling infections. Many of the body’s organs and tissues have receptors for vitamin D, and scientists are still teasing out its other possible functions.

 

New Vitamin D Research: Beyond Building Bones

Several promising areas of vitamin D research look far beyond vitamin D’s role in building bones. And, as you might expect, the news media release a flurry of reports every time another study links vitamin D to some new ailment. These reports can be confusing, however, because some studies are stronger than others, and any report needs to be interpreted in the light of all other evidence. More answers may come from randomized trials, such as the VITamin D and OmegA-3 TriaL (VITAL), which will enroll 20,000 healthy men and women to see if taking 2,000 IU of vitamin D or 1,000 mg of fish oil daily lowers the risk of cancer, heart disease, and stroke.

Here, we provide an overview of some of the more promising areas of vitamin D research, highlighting the complex role of vitamin D in disease prevention—and the many unanswered questions that remain.

 

Vitamin D and Bone and Muscle Strength

Vitamin D plays a definite role in bone health and reducing fractures; the central issue is, what is the minimum dose that is effective? Several randomized trials have shown that vitamin D supplementation prevents fractures—as long as it is taken in a high enough dose. (913)

 

NUTRITION IN-DEPTH

 

Why to Avoid Super High Doses of Vitamin D

A recent vitamin D trial drew headlines for its unexpected finding that a very high dose of vitamin D increased fracture and fall risk in older women. (18) The trial’s vitamin D dose—500,000 IU taken by mouth on a single day, once a year—was much higher than previously tested in an annual regimen.

There’s strong evidence that more moderate doses of vitamin D taken daily or weekly protect against fractures and falls—and are safe. Read more about this study’s findings, and why it makes sense to stick to more moderate vitamin D doses and avoid single, super high doses.

A summary of the evidence comes from a combined analysis of 12 fracture prevention trials that included more than 40,000 elderly people, most of them women. Researchers found that high intakes of vitamin D supplements—of about 800 IU per day—reduced hip and non-spine fractures by over 20 percent, while lower intakes (400 IU or less) failed to offer any fracture prevention benefit. (13)

Vitamin D 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. (1416)  Once again, vitamin D dose matters: A combined analysis of multiple studies found that taking 700 to 1,000 IU of vitamin D per day lowered the risk of falls by 19 percent, but taking 200 to 600 IU per day did not offer any such protection. (17)

Based on these fall- and fracture-prevention findings, the International Osteoporosis Foundation recommends that adults over age 60 aim for vitamin D blood levels of 30 ng/ml. (52) Most people will need vitamin D supplements of at least 800 to 1,000 IU per day, and possibly higher, to reach these levels.

 

Vitamin D and Heart Disease

The heart is basically a large muscle, and like skeletal muscle, it has receptors for vitamin D. (19) So perhaps it’s no surprise that studies are finding that inadequate vitamin D may be linked to heart disease. The Health Professional Follow-Up Study checked the vitamin D blood levels in nearly 50,000 men who were healthy, and then followed them for 10 years. (20) They found that men who were low in vitamin D were twice as likely to have a heart attack as men who had adequate levels of vitamin D. Other studies have found that low vitamin D levels were associated with higher risk of heart failure, sudden cardiac death, stroke, overall cardiovascular disease, and cardiovascular death. (2124) How exactly might vitamin D help prevent heart disease? There’s evidence that vitamin D plays a role in controlling blood pressure and preventing artery damage, and this may explain these findings. (25) Still, more research is needed before we can be confident of these benefits.

 

Vitamin D and Cancer

Nearly 30 years ago, researchers noticed an intriguing relationship between colon cancer deaths and geographic location: People who lived at higher latitudes, such as in the northern U.S., had higher rates of death from colon cancer than people who live closer to the equator. (26) The sun’s UVB rays are weaker at higher latitudes, and in turn, people’s vitamin D levels in these high latitude locales tend to be lower. This led to the hypothesis that low vitamin D levels might somehow increase colon cancer risk. (26)

 

Vitamin D and Geographic Location

Many scientific hypotheses about vitamin D and disease stem from studies that have compared solar radiation and disease rates in different countries. These can be a good starting point for other research but don’t provide the most definitive information…. Read more about vitamin D studies and geographic location.

Since then, dozens of studies suggest an association between low vitamin D levels and increased risks of colon and other cancers. (1,27)  The evidence is strongest for colorectal cancer, with observational studies consistently finding that the lower the vitamin D levels, the higher the risk is of these diseases. (2838) Vitamin D levels may also predict cancer survival, but evidence for this is still limited. (27) Yet finding such associations does not necessarily mean that taking vitamin D supplements will lower cancer risk.

The VITAL trial will look specifically at whether vitamin D supplements lower cancer risk. It will be years, though, before it releases any results. It could also fail to detect a real benefit of vitamin D, for several reasons: If people in the placebo group decide on their own to take vitamin D supplements, that could minimize any differences between the placebo group and the supplement group; the study may not follow participants for a long enough time to show a cancer prevention benefit; or study participants may be starting supplements too late in life to lower their cancer risk. In the meantime, based on the evidence to date, 16 scientists have circulated a “call for action” on vitamin D and cancer prevention: (27) Given the high rates of vitamin D inadequacy in North America, the strong evidence for reduction of osteoporosis and fractures, the potential cancer-fighting benefits of vitamin D, and the low risk of vitamin D supplementation, they recommend widespread vitamin D supplementation of 2,000 IU per day. (27) The

Canadian Cancer Society has also recommended that Canadian adults consider taking vitamin D supplements of 1,000 IU per day during the fall and winter; people who are at high risk of having low vitamin D levels (because they are older, have dark skin, spend little time in the sun, or cover up when they go outside) should consider taking supplements year round. (53)

 

Read more: vitamin D trials for cancer prevention

 

Vitamin D and Immune Function

Vitamin D’s role in regulating the immune system has led scientists to explore two parallel research paths: Does low vitamin D contribute to the development of multiple sclerosis, type 1 diabetes, and other so-called “autoimmune” diseases, where the body’s immune system attacks its own organs and tissues? And could vitamin D supplements help boost our body’s defenses to fight infectious disease, such as tuberculosis and seasonal flu? This is a hot research area and more findings will be emerging.

 

Vitamin D and Multiple Sclerosis: Multiple sclerosis (MS) rates are much higher far north (or far south) of the equator than in sunnier climes, and researchers suspect that chronic vitamin D inadequacy may be one reason why. One prospective study to look at this question found that among white men and women, those with the highest vitamin D blood levels had a 62 percent lower risk of developing MS than those with the lowest vitamin D levels. (39) The study didn’t find this effect among black men and women, most likely because there were fewer black study participants and most of them had low vitamin D levels, making it harder to find any link between vitamin D and MS if one exists.

 

Vitamin D and Type 1 Diabetes: Type 1 diabetes is another disease that varies with geography—a child in Finland is about 400 times more likely to develop it than a child in Venezuela. (40) Evidence that vitamin D may play a role in preventing type 1 diabetes comes from a 30-year study that followed more than 10,000 Finnish children from birth: Children who regularly received vitamin D supplements during infancy had a nearly 90 percent lower risk of developing type 1 diabetes than those who did not receive supplements. (41)  Other European case-control studies, when analyzed together, also suggest that vitamin D may help protect against type 1 diabetes. (42) No randomized controlled trials have tested this notion, and it is not clear that they would be possible to conduct.

 

Vitamin D, the Flu, and the Common Cold: The flu virus wreaks the most havoc in the winter, abating in the summer months. This seasonality led a British doctor to hypothesize that a sunlight-related “seasonal stimulus” triggered influenza outbreaks. (43) More than 20 years after this initial hypothesis, several scientists published a paper suggesting that vitamin D may be the seasonal stimulus. (44) Among the evidence they cite:

  • Vitamin D levels are lowest in the winter months. (44) 

  • The active form of vitamin D tempers the damaging inflammatory response of some white blood cells, while it also boosts immune cells’ production of microbe-fighting proteins. (44) 

  • Children who have vitamin D-deficiency rickets are more likely to get respiratory infections, while children exposed to sunlight seem to have fewer respiratory infections. (44) 

  • Adults who have low vitamin D levels are more likely to report having had a recent cough, cold, or upper respiratory tract infection. (45)

A recent randomized controlled trial in Japanese school children tested whether taking daily vitamin D supplements would prevent seasonal flu. (46) The trial followed nearly 340 children for four months during the height of the winter flu season. Half of the study participants received pills that contained 1,200 IU of vitamin D; the other half received placebo pills. Researchers found that type A influenza rates in the vitamin D group were about 40 percent lower than in the placebo group; there was no significant difference in type B influenza rates. This was a small but promising study, and more research is needed before we can definitively say that vitamin D protects against the flu. But don’t skip your flu shot, even if vitamin D has some benefit.

 

Vitamin D and Tuberculosis: Before the advent of antibiotics, sunlight and sun lamps were part of the standard treatment for tuberculosis (TB). (47) More recent research suggests that the “sunshine vitamin” may be linked to TB risk. Several case-control studies, when analyzed together, suggest that people diagnosed with tuberculosis have lower vitamin D levels than healthy people of similar age and other characteristics. (48)   Such studies do not follow individuals over time, so they cannot tell us whether low vitamin D levels led to the increased TB risk or whether taking vitamin D supplements would prevent TB. There are also genetic differences in the receptor that binds vitamin D, and these differences may influence TB risk. (49) Again, more research is needed. (49)

 

Vitamin D and Risk of Premature Death

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. (50) 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 and mortality. (51)

 

Why the IOM’s Vitamin D Recommendation Falls Short

Taken together, these disparate studies on bone health, heart disease, cancer, immune function, and early death add up to a powerful conclusion: Many people do not get enough vitamin D to protect their bones and minimize risk of falling—and taking vitamin D supplements of 1,000 to 2,000 IU per day would be a safe way to do both. This alone is good reason to consider taking a vitamin D supplement of 1,000 to 2,000 IU per day, and there is a strong likelihood of other benefits, even if not yet proven. Yet the IOM added up the evidence and reached a different conclusion—that children and most adults in the U.S. and Canada only need 600 IU of vitamin D a day. While the report notes that the 600 IU can come from food, supplements, or a combination of both, it acknowledges that very few Americans reach this intake.  Despite this, the committee recommended supplements for only a few special groups. There are several reasons why the IOM’s recommendation falls short:

 

Too Narrow a View of the Scientific Evidence

When evaluating the evidence on vitamin D, the IOM gave randomized clinical trials the most weight, since, in theory, such trials are the most rigorous: Researchers that randomly assign study participants to receive a treatment, such as a vitamin supplement, or a sugar pill (placebo), can be more certain that the treatment itself is responsible for any results.

But in reality, randomized clinical trials do not always offer the best evidence on vitamin supplements and health: They are expensive to conduct, so often they last only a few years, and they tend to enroll people who are already at a high risk of disease—for example, people who are older or who are not in the best health. As a result, these trials may be too short or too late in life to show the benefit of a vitamin supplement, if one exists.

Cohort studies can overcome some of the shortcomings of clinical trials, since they can follow large groups of initially-healthy people for long periods of time—long enough for links between vitamin levels and disease risks to emerge. Laboratory studies and animal studies also help fill in the research picture.
Most of the randomized trials of vitamin D have focused on bone health, and there’s been a lack of randomized trials on vitamin D and other chronic diseases. Unfortunately, the IOM committee interpreted this lack of trials as evidence of no benefit—in effect, ignoring the substantial evidence from cohort and other studies that vitamin D plays an important role in lowering the risk of several chronic diseases.

Based on this limited view, the IOM determined that most Americans have adequate blood levels of vitamin D—at least 20 nanograms per milliliter (ng/mL) or higher. Yet there’s much evidence that higher blood levels—on the order of 30 ng/mL—would do a better job of protecting bones, may help lower the risk of colon cancer and a host of diseases, and are safe. The safest and easiest way to achieve such blood levels is to take a supplement that contains at least 800 to 1,000 IU of vitamin D a day, and for people at high risk of low vitamin D levels, 2,000 IU a day.

 

Read more: why the IOM’s updated vitamin D and calcium guidelines are too low in vitamin D and too high in calcium for bone health

 

Too Hesitant on Vitamin D Supplements

Even if you accept the IOM’s lower criteria for adequate vitamin D blood levels (20 ng/mL)—and accept its findings that 600 IU of vitamin D per day is enough for most people to reach these blood levels—the report’s tepid recommendations on vitamin D supplements just do not make sense.

Q. What type of vitamin D is best?

Two forms of vitamin D are used in supplements: vitamin D2 (“ergocalciferol,” or pre-vitamin D) and vitamin D3 (“cholecalciferol”). Vitamin D3 is chemically indistinguishable from the form of vitamin D produced in the body…. Read more about what type of vitamin D is best.

 

The report recommends supplements for breastfed infants (and, especially, breastfed infants who have dark skin), since they are at high risk of deficiency. It also says that frail elderly who live in institutions should be monitored for vitamin D nutrition, and that a vitamin D “supplement is also an option” for people who do not eat dairy or animal products. But it does not explicitly advocate supplements for the population at large, or for other groups who are at risk of low vitamin D levels, such as people who are obese, who have dark skin, or who spend their winters in the northern states.

Yet data included with the IOM report, based on the National Health and Nutrition Examination Survey (which includes a representative sample of Americans), finds that 11 percent of European-Americans and 54 percent of African-Americans have blood vitamin D levels below 20 ng/mL. That means, in effect, that tens of millions of Americans have low vitamin D blood levels. These percentages would be even higher if one-third of Americans were not already taking vitamin D supplements in their multivitamins, and if the national survey had included winter samples from people living in the Northern states, since vitamin D levels are low at that time of year.

Very few Americans get the recommended 600 IU of vitamin D per day from food alone. The IOM committee acknowledges this—yet still concludes that Americans meet “average requirements” for vitamin D.  (Even the rationale for recommending 600 IU per day to achieve the low bar of 20 ng/mL is based on a flawed analysis by the IOM committee that considered the average blood level for a population; if the average is at 20 ng/mL, half of the population will be below that level. )

So how are Americans getting their vitamin D? The committee speculates that people get “at least some vitamin D from inadvertent or deliberate sun exposure.” Unprotected sun exposure, though, can increase the risk of skin cancer, and generally, it’s not recommended as a way to obtain vitamin D. Given that, it does not make sense for the committee to recommend a vitamin D intake that most people cannot get through food—while at the same time, giving only minimal guidance on who might really need vitamin D supplements.

 

Overstated Concern about High Vitamin D Blood Levels

In addition to understating the potential benefits of vitamin D and the need for supplements, the IOM overstated the concerns about having too-high blood levels of vitamin D.  For example, when the IOM committee looked at the relationship between vitamin D blood levels and premature death, it focused on data showing that at very high vitamin D blood levels—upwards of 70 ng/mL—mortality rates rise slightly. It glossed over data showing that mortality rates steadily drop as vitamin D levels rise, at least up to 40 ng/mL, and perhaps beyond: Since relatively few people have vitamin D levels higher than 40 ng/mL, there is not as much mortality data for levels in the 40–70 ng/mL range. Most studies suggest mortality continues to decrease—or does not increase—in the 40–70 ng/mL range, but a few studies have shown an increased mortality within this range.

As if to further justify its cautionary tone on vitamin D, the IOM’s press release pointed to other vitamin supplements—antioxidants like beta carotene and vitamin E, for example—that initially seemed promising for disease prevention but failed to pan out (and, sometimes, seemed to cause harm) in clinical trials. (54) Here too, though, the IOM’s logic is flawed: Beta carotene and vitamin E trials tested extremely high doses of those vitamins—ten to twenty times higher than what one might naturally get from a healthy diet. Vitamin D, though, is a different story: Spending a short time in the summer sun can produce the equivalent of 10,000 IU or more of vitamin D, and our evolutionary ancestors (who spent more time outdoors than we do, with less clothing) surely had much higher vitamin D levels than we typically have now.  By comparison, a vitamin D supplement of 1,000 to 2,000 IU a day is a very modest dose, and may be lower than optimal.

 

The Bottom Line: Many People Need Extra Vitamin D

Based on the evidence to date, it’s clear that many people don’t get enough vitamin D to protect their health. The International Osteoporosis Federation’s vitamin D recommendations, (52) though developed to prevent fall and fractures in older adults, offer a solid, evidence-based guidepost for younger and middle-aged adults, too: Taking a vitamin D supplement of 800 to 1,000 IU per day will help people, on average, achieve adequate blood levels of vitamin D (30 ng/mL). These vitamin D amounts are safe, falling well below the newly raised vitamin D upper limit of 4,000 IU per day—and they are easy to achieve, since more and more multivitamins now contain 800 to 1,000 IU of vitamin D. If your vitamin contains only 400 IU of vitamin D, consider adding an extra vitamin D supplement. People who are at high risk of deficiency, including people with darker skin, who are obese, or who spend little time in the sun, may need 2,000 IU of vitamin D (or more) to achieve adequate levels in the blood. If you fall into one of these groups, taking 2,000 IU of vitamin D each day is reasonable—and it’s an amount that falls well within the safe range. As always, it’s a good idea to discuss use of supplements with your doctor, and he or she may want to order a vitamin D blood test.

What makes the most sense from a public health point of view? It would be expensive to test everyone’s vitamin D blood levels, especially since the tests would need to be repeated seasonally. While people can make vitamin D from the sun, getting too much sun increases the risk of skin cancer, so it’s just not the best way to get vitamin D. By comparison, vitamin D supplements of 800 to 1,000 IU per day are inexpensive and safe—and provide a reasonable approach to avoiding D-ficiency.

 

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. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010; 121:297-300.

4. Robinson PD, Hogler W, Craig ME, et al. The re-emerging burden of rickets: a decade of experience from Sydney. Arch Dis Child. 2006; 91:564-8.

5. Kreiter SR, Schwartz RP, Kirkman HN, Jr., Charlton PA, Calikoglu AS, Davenport ML. Nutritional rickets in African American breast-fed infants. J Pediatr. 2000; 137:153-7.

6. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008; 122:398-417.

7. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press, 2010.

8. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004; 79:362-71.

9. 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.

10. 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.

11. Cauley JA, Lacroix AZ, Wu L, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008; 149:242-50.

12. Cauley JA, Parimi N, Ensrud KE, et al. Serum 25 HydroxyVitamin D and the Risk of Hip and Non-spine Fractures in Older Men. J Bone Miner Res. 2009.

13. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009; 169:551-61.

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

15. 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.

16. Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med. 2006; 166:424-30.

17. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009; 339:b3692.

18. Sanders KM, Stuart AL, Williamson EJ; et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815-1822.

19. Giovannucci E. Expanding roles of vitamin D. J Clin Endocrinol Metab. 2009; 94:418-20.

20. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008; 168:1174-80.

21. Pilz S, Marz W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008; 93:3927-35.

22. Pilz S, Dobnig H, Fischer JE, et al. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke. 2008; 39:2611-3.

23. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117:503-11.

24. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008; 168:1340-9.

25. Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008; 29:361-8.

26. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980; 9:227-31.

27. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009; 19:468-83.

28. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther. 2009; 30:113-25.

29. 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.

30. Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007; 32:210-6.

31. Giovannucci E. Epidemiological evidence for vitamin D and colorectal cancer. J Bone Miner Res. 2007; 22 Suppl 2:V81-5.

32. Lin J, Zhang SM, Cook NR, Manson JE, Lee IM, Buring JE. Intakes of calcium and vitamin D and risk of colorectal cancer in women. Am J Epidemiol. 2005; 161:755-64.

33. Huncharek M, Muscat J, Kupelnick B. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutr Cancer. 2009; 61:47-69.

34. Bertone-Johnson ER, Chen WY, Holick MF, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14:1991-7.

35. Garland CF, Gorham ED, Mohr SB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007; 103:708-11.

36. Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007; 167:1050-9.

37. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007; 18:775-82.

38. Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2008; 17:889-94.

39. 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.

40. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. 2006; 175:165-70.

41. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358:1500-3.

42. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008; 93:512-7.

43. Hope-Simpson RE. The role of season in the epidemiology of influenza. J Hyg (Lond). 1981; 86:35-47.

44. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006; 134:1129-40.

45. Ginde AA, Mansbach JM, Camargo CA, Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009; 169:384-90.

46. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 91:1255-60. Epub 2010 Mar 10.

47. Zasloff M. Fighting infections with vitamin D. Nat Med. 2006; 12:388-90.

48. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008; 37:113-9.

49. Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutr Rev. 2009; 67:289-93.

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

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

52. Dawson-Hughes B, Mithal A, Bonjour JP,  et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010. 21:1151-4.

53. Canadian Cancer Society.  Canadian Cancer Society Announces Vitamin D Recommendation. 2007. Accessed March 24, 2011.

54. National Academies. Press Release: IOM Report Sets New Dietary Intake Levels for Calcium and Vitamin D To Maintain Health and Avoid Risks Associated With Excess. November 30, 2010. Accessed March 24, 2011.

Fonte

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-d/#vitamin-d-recommendations

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-d/

2 Respostas

  1. […] Parabens and Breast Cancer, Read the Labels!CCNewsPossible 75% Cancer Mortality Reduction with Vitamin DHMC mulls cancer tests on women over 40 – Peninsula OnThe Teal before the Pink: Ovarian Cancer Awareness MonthPIP breast implants do not cause cancer, UK rulesThe Nutrition Source – Vitamin D and Health […]

  2. […] Case-Control Study Among US VeteransNew breast cancer blood test141 Reasons Sugar Ruins Your HealthThe Nutrition Source – Vitamin D and Health // IE Evitar seleccion de texto document.onselectstart=function(){ if […]

Deixe um comentário

Preencha os seus dados abaixo ou clique em um ícone para log in:

Logotipo do WordPress.com

Você está comentando utilizando sua conta WordPress.com. Sair / Alterar )

Imagem do Twitter

Você está comentando utilizando sua conta Twitter. Sair / Alterar )

Foto do Facebook

Você está comentando utilizando sua conta Facebook. Sair / Alterar )

Foto do Google+

Você está comentando utilizando sua conta Google+. Sair / Alterar )

Conectando a %s

%d blogueiros gostam disto: