Vitamin D Supplementation: An Update

Christine Gonzalez, PharmD, CHHC

Disclosures

US Pharmacist 

In This Article

Disease Prevention

Cancer

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.

Heart Disease

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.

Fractures and Falls

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.

Autoimmune Diseases and Influenza

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.

Type 2 Diabetes and Depression

Some studies have shown that vitamin D may lower the risk of type 2 diabetes, but few studies have examined the effect of vitamin D on depression. A trial of nondiabetic patients aged 65 years and older found that those who received 700 IU of vitamin D (plus calcium) had a smaller rise in fasting plasma glucose over 3 years versus those who received placebo.[24] A Norwegian trial of overweight subjects showed that those receiving a high dose of vitamin D (20,000 or 40,000 IU weekly) had a significant improvement in depressive symptom scale scores after 1 year versus those receiving placebo.[25] These results need to be replicated in order to determine a correlation between vitamin D and the risk of diabetes or depression.

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