Vitamin D is a fat-soluble vitamin that acts as a steroid hormone. The body makes vitamin D from cholesterol through a process triggered by the action of the sun's ultraviolet B rays on the skin (FIGURE 1). Factors such as skin color, age, amount and time of sun exposure, and geographic location affect how much vitamin D the body makes. Vitamin D influences the bones, intestines, immune and cardiovascular systems, pancreas, muscles, brain, and the control of cell cycles.[6] Its primary functions are to maintain normal blood concentrations of calcium and phosphorus and to support bone health.
 | Figure 1. Vitamin D synthesis. |
Risk factors for vitamin D deficiency include living in northern latitudes (in the U.S., above the line from San Francisco to Philadelphia), failing to get at least 15 minutes of direct sun exposure daily, being African American or dark-skinned, being elderly, or being overweight or obese.[5] Rickets and osteomalacia are the well-known diseases of severe vitamin D deficiency. Musculoskeletal pain and periodontal disease may also indicate a significant vitamin D deficiency.[7] Subtle symptoms of milder deficiency include loss of appetite, diarrhea, insomnia, vision problems, and a burning sensation in the mouth and throat.[7] Drawing a blood calcidiol concentration is the standard test for vitamin D status, since calcidiol has a longer half-life.[8]
Vitamin D decreases cell proliferation and increases cell differentiation, stops the growth of new blood vessels, and has significant anti-inflammatory effects. Many studies have suggested a link between low vitamin D levels and an increased risk of cancer, with the strongest evidence for colorectal cancer. A Creighton University study found that postmenopausal women given 1,100 IU of vitamin D3 (plus calcium) versus placebo were 77% less likely to be diagnosed with cancer over the next 4 years.[10] In the Health Professionals Follow-up Study (HPFS), subjects with high vitamin D concentrations were half as likely to be diagnosed with colon cancer as those with low concentrations.[11]
Some studies have shown less positive results, however. The Women's Health Initiative found that women taking 400 IU of vitamin D3 (plus calcium) versus placebo did not have a lower risk of breast cancer.[12] Many critics have argued that this dosage of vitamin D is too low to prevent cancer. A 2006 Finnish study of male smokers found that those with higher vitamin D concentrations had a threefold increased risk for pancreatic cancer, with cigarette smoking not found to be a confounding factor.[13] A 2009 U.S. study of men and women (mostly nonsmokers) did not confirm these results, finding no association between vitamin D concentrations and pancreatic cancer overall, except in subjects with low sun exposure.[14] In this subgroup, higher versus lower vitamin D concentrations had a positive association with pancreatic cancer.[14] A definitive conclusion cannot yet be made about the association between vitamin D concentration and cancer risk, but results from many studies are promising.
Several studies are providing evidence that the protective effect of vitamin D on the heart could be via the renin-angiotensin hormone system, through the suppression of inflammation, or directly on the cells of the heart and blood-vessel walls. In the Framingham Heart Study, patients with low vitamin D concentrations (<15 ng/mL) had a 60% higher risk of heart disease than those with higher concentrations.[15] The HPFS found that subjects with low vitamin D concentrations (<15 ng/mL) were two times more likely to have a heart attack than those with high concentrations (>30 ng/mL).[16] In another study, which followed men and women for 4 years, patients with low vitamin D concentrations (<15 ng/mL) were three times more likely to be diagnosed with hypertension than those with high concentrations (>30 ng/mL).[17] As is the case with cancer and vitamin D, more studies are needed to determine the role of vitamin D in preventing heart disease, but the evidence thus far is positive.
Vitamin D is known to help the body absorb calcium, and it plays a role in bone health. Also, vitamin D receptors are located on the fast-twitch muscle fibers, which are the first to respond in a fall.[18] It is theorized that vitamin D may increase muscle strength, thereby preventing falls.[5] Many studies have shown an association between low vitamin D concentrations and an increased risk of fractures and falls in older adults.
A combined analysis of 12 fracture-prevention trials found that supplementation with about 800 IU of vitamin D per day reduced hip and nonspinal fractures by about 20%, and that supplementation with about 400 IU per day showed no benefit.[19] Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University have examined the best trials of vitamin D versus placebo for falls. Their conclusion is that "fall risk reduction begins at 700 IU and increases progressively with higher doses."[18] Overall, the evidence is strong in support of supplementing with vitamin D to prevent fractures and falls.
Since vitamin D has a role in regulating the immune system and a strong anti-inflammatory effect, it has been theorized that vitamin D deficiency could contribute to autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, and autoimmune thyroid disease. Scientists have suggested that vitamin D deficiency in the winter months may be the seasonal stimulus that triggers influenza outbreaks in the winter.[20] Numerous trials have evaluated the association between vitamin D and immune-system diseases.
A prospective study of white subjects found that those with the highest vitamin D concentrations had a 62% lower risk of developing MS versus those with the lowest concentrations.[21] A Finnish study that followed children from birth noted that those given vitamin D supplements during infancy had a nearly 90% lower risk of developing type 1 diabetes compared with children who did not receive supplements.22 In a Japanese randomized, controlled trial, children given a daily vitamin D supplement of 1,200 IU had a 40% lower rate of influenza type A compared with those given placebo; there was no significant difference in rates of influenza type B.[23] More studies of the influence of vitamin D on immunity will be emerging, as this is an area of great interest and it remains unclear whether there is a link.
Only a few foods are a good source of vitamin D. These include fortified dairy products and breakfast cereals, fatty fish, beef liver, and egg yolks. Besides increasing sun exposure, the best way to get additional vitamin D is through supplementation. Traditional multivitamins contain about 400 IU of vitamin D, but many multivitamins now contain 800 to 1,000 IU. A variety of options are available for individual vitamin D supplements, including capsules, chewable tablets, liquids, and drops. Cod liver oil is a good source of vitamin D, but in large doses there is a risk of vitamin A toxicity.[26]
While considerable research supports the importance of vitamin D beyond bone health, further trials are required before broad claims can be made about vitamin D and prevention of chronic disease. The Institute of Medicine (IOM) is reviewing the research on vitamin D and plans to report in late 2010 regarding any updates to the DRIs for vitamin D (and calcium).[30] Specifically, the IOM will consider the relation of vitamin D to cancer, bone health, and other chronic diseases.[30] An important study, the Vitamin D and Omega-3 Trial, was launched in early 2010 to determine whether 2,000 IU of vitamin D3 and 1,000 mg of EPA (eicosopentaenoic acid) plus DHA (docosahexaenoic acid) daily can lower the risk of cancer, heart disease, stroke, and other diseases.[31] This randomized trial, which will enroll about 20,000 healthy men and women, should provide more insight on vitamin D supplementation.
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