New Study Raises Further Questions About the Benefits of Vitamin D Supplementation in a Healthy Population
By Jessica Pyhtila, PharmD, BCGP, BCPS
A recent study in the Journal of the American Medical Association has raised questions about the effect of higher doses of Vitamin D on bone health. The trial adds to an existing body of literature suggesting that Vitamin D supplementation may only have a benefit on bone health in the setting of overt Vitamin D deficiency (1).
The study was a randomized clinical three-year trial of Vitamin D supplementation in 311 healthy adults conducted from 2013 to 2017 (1). The baseline 25(OH)D levels ranged from 30 to 125 nmol/L. Patients were divided into three groups. One group received vitamin D 400 IU daily, another received 4000 IU daily, and the third received 10000 IU daily. After three years, the mean 25(OH)D level was 77.4 nmol/L (30.8 ng/mL) in the 400 IU daily group, 132.2 nmol/L (52.8 ng/mL) in the 4000 IU daily group, and 144.4 4 nmol/L (57.6 ng/mL) in the 10000 IU daily group (2). Radial and tibial bone mineral density (BMD) were tested in all groups. After three years, patients taking 4000 IU or 10000 IU daily had a significantly lower radial BMD than patients taking a 400 IU daily dose of Vitamin D. Further, tibial BMD was significantly lower in patients taking 10000 IU daily. Bone strength was not impacted by Vitamin D intake in the study. Therefore, the trial found that high-dose Vitamin D supplementation was not beneficial to bone health.
Multiple sets of guidelines exist addressing Vitamin D therapy to achieve optimal serum 25-hydroxyvitamin D, or 25(OH)D levels. Organizations such as The Endocrine Society, The Institute of Medicine, The Mayo Clinic, The American Association of Clinical Endocrinologists and the American Geriatrics Society have all weighed in on the issue, with varying opinions (3,4). In general, the optimal 25(OH)D level across guidelines is 30 ng/mL or above. However, it remains unclear how far above this threshold is desirable or safe for patients. Complicating matters, guidelines additionally vary on optimal monitoring frequency, or even if monitoring should take place (4).
Known risks of Vitamin D include hypercalcemia with subsequent damage to the heart, kidneys and vasculature. Toxicity is thought to be limited to serum levels higher than 200 ng/mL (5). However, based on recent data, the Institute of Medicine now recommends to avoid 25(OH)D levels of greater than 50–60 ng/mL, because data suggest that serum levels as low as 30–48 ng/mL are linked to increases in all-cause mortality, pancreatic cancer, cardiovascular events, and falls and fractures in the elderly (5).
Therefore, the risks and benefits of Vitamin D supplementation in people without deficiency remain unclear. Future studies may help to clarify which patients may benefit from supplementation, versus which patients may be at health risks from it.
Sources:
- Burt, Lauren A; et al. “Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial.” August 27, 2019. Accessed December 29, 2019. Retrieved from: https://jamanetwork.com/journals/jama/article-abstract/2748796
- Com. “Convert [ nmol/l ] -> [ ng/ml ] for Vitamin D (25-Cholecalciferol).” (n.d.) Accessed December 29, 2019. Retrieved from: http://www.vitamindservice.com/node/91
- American Association of Clinical Endocrinologists. “Vitamin D Deficiency.” 2019. Accessed December 29, 2019. Retrieved from: https://www.aace.com/sites/default/files/2019-02/Vitamin_D_Deficiency_formatted.pdf
- American Geriatrics Society. “Recommendations Abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences.” December 18, 2013. Accessed December 29, 2019. Retrieved from: https://onlinelibrary.wiley.com/doi/full/10.1111/jgs.12631
- National Institutes of Health. “Vitamin D.” August 7, 2019. Accessed December 29, 2019. Retrieved from: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
