Vitamin D and Health
Table of Contents
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, 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. (- ) 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. ( - )
Why are these widespread vitamin D deficiencies of such 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, , , and multiple sclerosis, as well as , such as and even the .
Currently, there’s scientific debate about how much vitamin D people need each day. The Institute of Medicine, in a long-awaited report released on November 30, 2010 recommends tripling the daily vitamin D intake for children and adults in the U.S. and Canada, to 600 IU per day. () 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.
Read more about why the IOM’s new vitamin D and calcium guidelines are too low in vitamin D and too high in calcium for bone health.
Vitamin D is both a nutrient we eat and a hormone our bodies make. Few, so the biggest dietary sources of vitamin D are fortified foods and . 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 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.
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.
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 some people do not make enough, 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. (
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
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 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.
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(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.
Several studies link low vitamin D levels with an increased risk of fractures in older adults, and they suggest that vitamin D supplementation may prevent such fractures—as long as it is taken in a high enough dose. (- )
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 20 percent, while lower intakes (400 IU or less) failed to offer any fracture prevention benefit. ()
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. (- ) 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. ( )
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. () The trial’s vitamin D dose—500,000 IU taken in a once-a-year pill—was much higher than previously tested in an annual regimen. After up to 5 years of treatment, women in the vitamin D group had a 15 percent higher fall risk and a 26 percent higher fracture risk than women who received the placebo.
It’s possible that giving the vitamin D in one large dose, rather than in several doses spread throughout the year, led to the increased risk. () The study authors note that only one other study—also a high-dose, once-a-year regimen—found vitamin D to increase fracture risk; no other studies have found vitamin D to increase the risk of falls. Furthermore, there’s strong evidence that more moderate doses of vitamin D taken daily or weekly protect against fractures and falls—and are safe.
So what is the significance of this study for people who want to take vitamin D supplements? A reasonable conclusion would be to continue taking moderate doses of vitamin D regularly, since these have a strong safety record, but to avoid extremely high single doses. This recent finding does present a challenge to scientists who will work to understand why the extreme single dose appears to have adverse effects.
The heart is basically a large muscle, and like skeletal muscle, it has receptors for vitamin D. () So perhaps it’s no surprise that studies are finding vitamin D deficiency 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. ( ) They found that men who were deficient 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. ( - ) 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. ( ) Still, more research is needed before we can be confident of these benefits.
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. () 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. 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. (
Since then, dozens of studies suggest an association between low vitamin D levels and increased risks of colon and other cancers. (, ) The evidence is strongest for colorectal cancer, with most (but not all) observational studies finding that the lower the vitamin D levels, the higher the risk of these diseases. ( - ) Vitamin D levels may also predict cancer survival, but evidence for this is still limited. ( ) Yet finding such associations does not necessarily mean that taking vitamin D supplements will lower cancer risk.
Thetrial 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: ( ) Given the high rates of vitamin D deficiency 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 2000 IU per day. ( )
Vitamin D’s role in regulating the immune system has led scientists to explore two parallel research paths: Does vitamin D deficiency 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 deficiencies 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. ( ) 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. ( ) 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. ( ) Other European case-control studies, when analyzed together, also suggest that vitamin D may help protect against type 1 diabetes. ( ) 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. ( ) More than 20 years after this initial hypothesis, several scientists published a paper suggesting that vitamin D may be the seasonal stimulus. ( ) Among the evidence they cite:
- Vitamin D levels are lowest in the winter months. ( )
- 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. ( )
- 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. ( )
- Adults who have low vitamin D levels are more likely to report having had a recent cough, cold, or upper respiratory tract infection. ( )
A recent randomized controlled trial in Japanese school children tested whether taking daily vitamin D supplements would prevent seasonal flu. () 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). ( ) 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. ( ) Such studies do not follow individuals over time, so they cannot tell us whether vitamin D deficiency 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. ( ) Again, more research is needed. ( )
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 and mortality. ( )
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.. 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.. 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.
The aim of the Harvard School of Public Health Nutrition Source is to provide timely information on diet and nutrition for clinicians, allied health professionals, and the public. The contents of this Web site are not intended to offer personal medical advice. You should seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this Web site. The information does not mention brand names, nor does it endorse any particular products.