Vitamin D threshold varies with season, study shows

Researchers from the University of Washington have identified a threshold concentration of serum 25-hydroxyvitamin D [25-(OH)D] that is associated with increased risk for major medical events and say that season-specific targets may be more appropriate than static targets when evaluating health risk.

The results of the study were published May 1 in the Annals of Internal Medicine.

“Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D], which reflect total vitamin D intake from cutaneous synthesis and dietary consumption, are used to define vitamin D deficiency,” wrote lead author Ian de Boer, MD, assistant professor of medicine in the Division of Nephrology and a member of the Kidney Research Institute, University of Washington, and colleagues. However, different threshold recommendations exist, some at 75 nmol/L (20 and 30 ng/mL).

To address this controversy, the researchers examined the 25-(OH)D threshold concentrations associated with major clinical disease risk. The researchers measured 25(OH)D concentrations in a sample of 1,621 white adults who had enrolled in the Cardiovascular Health Study. The primary outcome was time to first occurrence of incident hip fracture, heart attack, incident of cancer, or death. Median follow-up was 11 years during which the primary outcome occurred in 63% of patients.

The researchers first noted that baseline 25-(OH)D concentration varied strongly by season with low season-specific 25-(OH)D concentration more common among women and patients at more northern study sites. In addition, it was associated with higher body mass index, hypertension, reduced physical activity, and higher circulating concentrations of parathyroid hormone.

They then identified threshold 25-(OH)D concentrations optimally associated with risk for the primary outcomes: 43 nmol/L (17 ng/mL) January through March, 50 nmol/L (20 ng/mL) April through June, 61 nmol/L (24 ng/mL) July through September, and 55 nmol/L (22 ng/mL) October through December.

Based on statistical analysis, the investigators found that the risk of major clinical disease rose when 25-(OH)D concentrations fell below 50 nmol/L (20ng/mL). Further, they noted that 30.5% of patients in the study had a 25-(OH)D concentration less than the season-specific threshold centered near 50 nmol/L (20 ng/mL), which they said was in line with other populations and emphasizes the large number of people at risk for potential complications.

The researchers say their data supports a threshold centered near 50 nmol/L (20 ng/mL), which is the level recently recommended by the Institute of Medicine, but further study should focus on whether vitamin D deficiency is causally related to non-bone outcomes. However, they suggest that season-specific targets for 25-(OH)D concentration appear to be more appropriate than static targets when considering potential health risks.

Primary funding for this study came from the National Institutes of Health.