Vitamin D: Is It the Best Thing Under the Sun?

Robert Finn; Deborah Flapan; Darbe Rotach Contributor Information

February 7, 2013

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Explosion of Research

The number of research studies on vitamin D has soared in recent years. Citations of studies involving vitamin D increased from 1142 in the year 2000 to 3877 in 2012. In comparison, citations for research on vitamin A and vitamin C have remained more or less level. The sun may not be the best way to get vitamin D, but the evidence may yet show that vitamin D is the best thing under the sun.

Slide 1.

The Vitamin That's Not a Vitamin

The fourth vitamin to be discovered, vitamin D is a group of secosteroid compounds that include ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). The term "vitamin" is generally reserved for vital substances the body cannot synthesize on its own. Given cholesterol and sunshine, the body can synthesize its own vitamin D, so it's not technically an essential dietary vitamin.

Serious deficiencies in vitamin D can lead to rickets, and it was research into this childhood disease, the pediatric form of osteomalacia, that led to the vitamin's 1922 discovery by Edward Mellanby. Illustration courtesy of Wiki Commons

Slide 2.

Vitamin D and Bone

Vitamin D has long been known to play an important role in bone health, and several recent studies provided additional confirmation. One study[1] suggested that low levels of vitamin D increase the risk for forearm fracture in children, and another[2] showed that girls who consumed the most vitamin D had the lowest risk for stress fractures. It's not just children who are at risk: 44% of postmenopausal women treated for distal radius fracture were vitamin D deficient or insufficient. And a meta-analysis[3] showed that high doses of vitamin D lower the risk for fracture by 14% to 30% in people age 65 years or older. Photo courtesy of Wiki Commons

Slide 3.

Vitamin D and Respiratory Infections?

If Linus Pauling were alive today, perhaps he would turn his attention away from vitamin C and write "Vitamin D and the Common Cold."

One randomized controlled trial[4] suggested that vitamin D supplementation reduced acute respiratory tract infections in children during the long, cold, and dark Mongolian winter. Another randomized controlled trial[5] showed that vitamin D reduced symptoms and antibiotic use in a group of patients with an increased frequency of respiratory infections. On the other hand, a third randomized controlled trial[6] showed no effect of vitamin D on reducing the incidence or severity of respiratory infection in healthy adults. Photo courtesy of Thinkstock

Slide 4.

Links to Diabetes

Low levels of vitamin D have been linked to several types of diabetes. A study[7] conducted in Australia found that children with type1 diabetes are more likely to have low levels of vitamin D. It's unclear, however, whether low levels of vitamin D caused the diabetes or vice versa. A larger study,[8] in active-duty military personnel in the United States, found that those with low levels of vitamin D were more likely to develop insulin-requiring diabetes within 1 year. And women who have low vitamin D levels during their first trimester of pregnancy were more likely to develop gestational diabetes. Photo courtesy of Thinkstock

Slide 5.

Vitamin D and Cardiovascular Disease

Numerous epidemiologic studies, including the largest one to date,[9] suggest that a low vitamin D level increases the risk for cardiovascular disease. But there may be a threshold effect,[10] with heart health improving as circulating vitamin D levels increase from 20 to 60 nmol/L, followed by a plateau or perhaps even an increase in risk at higher levels. Unfortunately, a randomized controlled trial among older women failed to find evidence that vitamin D supplementation[11] improved markers of heart health. Photo courtesy of Thinkstock

Slide 6.

Obesity

Women with low levels of vitamin D during pregnancy[12] may have children that are more prone to excess body fat at age 6 years. Furthermore, children ages 6 to 18 years[13] who are overweight are more likely to have low vitamin D levels. Adequate levels of vitamin D are associated with less weight gain among women age 65 and older.[14] Photo courtesy of Thinkstock

Slide 7.

Vitamin D and Cancer

Less information has been published about connections between vitamin D and cancer, but some developments have occurred in the past year. In a result the researchers termed "unexpected," women with breast cancer who were being treated with zoledronic acid for bone complications had a lower risk for bone recurrence if they had sufficient vitamin D levels. Vitamin D supplementation may help breast cancer survivors adhere to adjuvant treatment with aromatase inhibitors. And differences in vitamin D–related genes may contribute to increased susceptibility to colon cancer among black Americans. Photo courtesy of Wiki Commons

Slide 8.

Neurologic Function

Vitamin D has been tied to several higher neurologic functions. Studies have linked autism to low vitamin D during pregnancy, a connection that was strengthened by a map showing that autism rates were highest among children living in states with the lowest levels of ultraviolet B radiation.[15] People with Alzheimer's disease tend to have low levels of vitamin D, and better cognitive test results are linked to higher vitamin D levels.[16] Vitamin D3 may help clear the brain of amyloid-β.[17] And low vitamin D levels in pregnant women have been associated with poor language development in their offspring.[18] Photo courtesy of Thinkstock

Slide 9.

Stroke and Multiple Sclerosis

Data from the Honolulu Heart Program show that people with low dietary vitamin D at baseline were about 25% more likely to sustain thromboembolic stroke, but not hemorrhagic stroke, during the ensuing 34 years.[19]

The last year has seen a flurry of studies linking vitamin D to multiple sclerosis (MS), and all of them tie low levels of vitamin D to the disease. Three of these studies were published in a single issue of the journal Neurology. Another study linked low levels of vitamin D plus exposure to the Epstein-Barr virus to the development of MS.[20] Low vitamin D levels predict a near-term conversion of clinically isolated syndromes to definite MS. And the risk of developing MS has been linked to lower sun exposure in early life. Photo courtesy of Wiki Commons

Slide 10.

Pain

About half of women prescribed aromatase inhibitors for metastatic breast cancer suffer intense musculoskeletal pain,[21] but high-dose vitamin D2 supplements appear to help. A single oral dose of 300,000 IU of vitamin D appears to help with dysmenorrhea.[22] And a low level of vitamin D in black Americans increases the risk for knee osteoarthritis pain.[23] Photo courtesy of Thinkstock

Slide 11.

Lung Disorders

High-dose vitamin D may speed tuberculosis recovery.[24] And low vitamin D levels appear to be linked to the need for steroids in asthma and may also blunt the effectiveness of asthma treatment.[25]

For chronic obstructive pulmonary disease, however, the story isn't as clear cut. According to one study, high-dose vitamin D supplementation improves exercise capacity and respiratory muscle strength during rehabilitation. But according to another, high-dose supplements failed to prevent exacerbations or secondary outcomes.[26] Photo courtesy of Wiki Commons

Slide 12.

Gastrointestinal Disorders

Women with sufficient vitamin D levels at baseline are 62% less likely to develop Crohn's disease over 22 years than those with vitamin D insufficiency.[27]

Women living at southern latitudes in the United States are 52% less likely to have inflammatory bowel disease than those living in the north.[28] Photo courtesy of Wiki Commons

Slide 13.

Kidney Disease

Vitamin D deficiency is almost universal among patients with chronic kidney disease (CKD).[29] Two recent studies independently concluded that high-dose cholecalciferol (vitamin D3) supplementation safely prevents[30] and corrects this in patients undergoing dialysis. Vitamin D supplementation also lowers hepcidin levels in patients with CKD. Photo courtesy of Wiki Commons

Slide 14.

But Wait, There's More

Within the past year, studies have shown that vitamin D may reduce risk for dental caries,[31] low vitamin D may be a result of depression,[32] vitamin D deficiency increases risk for perforated eardrums, and low vitamin D is linked to food allergy. And the list goes on. Photos courtesy of Wiki Commons(L); Thinkstock

Slide 15.

How Much Is Enough?

There's little consensus about what blood levels of vitamin D are adequate, and even less on how much supplementation is enough. The Institute of Medicine says blood levels should be 20 ng/mL, but the Endocrine Society sets the level at 30 ng/mL. The US Recommended Dietary Allowance is 600 IU for people ages 1 to 70 years and 800 IU for those who are older. Some authorities recommend that people who are deficient should receive supplements of 1000 to 2000 IU daily, but others have recommended single-bolus doses of up to 500,000 IU. Photo courtesy of Thinkstock

Slide 16.

How to Measure?

If there's little agreement on how much vitamin D we need, there's even less on how to measure blood levels. You can choose an old, slow, but accurate method, or you can choose one of several new and fast but wildly inaccurate methods. According to one study, these rapid tests may be inaccurate as much as 40% of the time, most often characterizing patients as vitamin D deficient when they're not. Photo courtesy of Thinkstock

Slide 17.

Elixir of Life?

While vitamin D appears to be involved in almost every body system, some researchers are looking at the big picture — overall mortality. Oral active vitamin D is associated with reduced all-cause mortality in patients undergoing peritoneal dialysis. Vitamin D has also been linked to lower mortality in patients with pneumonia.[33] And a large meta-analysis found that increased intake of vitamin D plus calcium, but not vitamin D alone, is linked to a decrease in all-cause mortality among elderly patients.[34] Photo courtesy of Thinkstock

Slide 18.

And Now for Something Completely Different

So if you've been paying attention to the previous slides, they nearly all seem to point in one direction: Lower levels of vitamin D bad, higher levels good or neutral. Case closed? Maybe not. A recent study suggests that some people with a genetic predisposition to longevity have a reduced frequency of a gene variant that predisposes people to high vitamin D levels. They also have lower levels of vitamin D.[35] If only science gave us simple, unambiguous answers! Photo courtesy of Thinkstock

Slide 19.

Contributor Information

Robert Finn
Assignment Editor, Medscape Medical News, San Francisco, California

Deborah Flapan
Director, Medscape Medical News, Chicago, Illinois

Darbe Rotach
Medscape Senior Photo Editor, New York City

References

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  2. Sonneville KR, Gordon CM, Kocher MS, et al. Vitamin D, calcium, and dairy intakes and stress fractures among female adolescents. Arch Pediatr Adolesc Med. 2012;166:595-600. doi:10.1001/archpediatrics.2012.5. Abstract
  3. Bischoff-Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012367:40-49. Abstract
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  17. Mizwicki MT, Menegaz D, Zhang J, et al. Genomic and nongenomic signaling induced by 1a,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer's disease macrophages. J Alzheimers Dis. 2012;29:51-62. Abstract
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  26. Lehouck A, Mathieu C, Carremans C, et al. High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2012;156:105-114. Full Text
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  32. Kjærgaard M, Waterloo K, Wang CE, et al. Effect of vitamin D supplement on depression scores in people with low levels of serum 25-hydroxyvitamin D: nested case-control study and randomised clinical trial. Br J Psychiatry. 2012;201:360-368. Abstract
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  34. Rejnmark L, Avenell A, Masud T, et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab. 2012;97:2670-2681. Abstract
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