Potential immune benefits of strong vitamin D status in healthy individuals

The study, published online in PLOS ONE, reveals for the first time that improvement in the vitamin D status of healthy adults significantly impacts genes involved with a number of biologic pathways associated with cancer, cardiovascular disease (CVD), infectious diseases and autoimmune diseases. While previous studies have shown that vitamin D deficiency is associated with an increased risk for the aforementioned diseases, these results go a step further and provide direct evidence that improvement in vitamin D status plays a large role in improving immunity and lowering the risk for many diseases.

Vitamin D is unique in that it can be both ingested and synthesized by the body with sun exposure. It is then converted by both the liver and kidneys to a form that the body can use. An individuals' level of vitamin D, or their vitamin D status, is determined by measuring the level of 25-hydroxyvitamin D in the blood. Vitamin D deficiency, which is defined as a status of less than 20 nanograms per milliliter (ng/mL) of 25-hydroxyvitamin D, can cause a number of health issues, including rickets and other musculoskeletal diseases. Recently, however, data suggests that vitamin D deficiency (<20 ng/mL) and vitamin D insufficiency (between 21-29 ng/mL) is linked to cancer, autoimmune diseases, infectious diseases, type 2 diabetes and cardiovascular disease.

The randomized, double-blind, single-site pilot trial involved eight healthy men and women with an average age of 27 who were vitamin D deficient or insufficient at the start of the trial. Three participants received 400 International Units (IUs) of vitamin D per day and five received 2,000 IUs per day for a two-month period. Samples of white blood cells (immune cells) were collected at the beginning of the two-month period and again at the end. A broad gene expression analysis was conducted on these samples and more than 22,500 genes were investigated to see if their activity increased or decreased as a result of the vitamin D intake.

At the end of the pilot, the group that received 2000 IUs achieved a vitamin D status of 34 ng/mL, which is considered sufficient, while the group that received 400 IUs achieved an insufficient status of 25 ng/mL.

The results of the gene expression analysis indicated statistically significant alterations in the activity of 291 genes. Further analysis showed that the biologic functions associated with the 291 genes are related to 160 biologic pathways linked to cancer, autoimmune diseases, infectious diseases and CVD.

Examining gene response elements, or sequences of DNA bases that interact with vitamin D receptors to regulate gene expression, they also identified new genes related to vitamin D status. To ensure that their observations were accurate, the researchers looked at 12 genes whose level of expression does not change, and those genes remained stable throughout the trial period.

"This study reveals the molecular fingerprints that help explain the non-skeletal health benefits of vitamin D," said Michael F. Holick, PhD, MD, professor of medicine, physiology and biophysics at BUSM and leading vitamin D expert who served as the study's corresponding author. "While a larger study is necessary to confirm our observations, the data demonstrates that improving vitamin D status can have a dramatic effect on gene expression in our immune cells and may help explain the role of vitamin D in reducing the risk for CVD, cancer and other diseases."