Clinical Guidelines for the Use of Vitamin D: Empirical Supplementation and 25(OH)D Testing for Disease Prevention
Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and various common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases.
Although a causal link between serum 25(OH)D concentrations and many of these disorders has not been established, these associations have led to widespread vitamin D supplementation and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increased vitamin D use is unclear, and the optimal vitamin D intake and the role of 25(OH)D testing for disease prevention remain uncertain.
The objective was to develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing.
A multidisciplinary panel of clinical experts and experts in guideline methodology and systematic literature review identified and prioritized 14 clinically relevant questions regarding the use of vitamin D and 25(OH)D testing to lower the risk of disease.
The panel prioritized randomized placebo-controlled trials in general populations (without established indications for vitamin D treatment or 25[OH]D testing), evaluating the effects of empirical vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined “empirical supplementation” as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D.
Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations.
The approach incorporated the perspectives of a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and the impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRIs for vitamin D.
Results suggested empirical vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to reduce the risk of respiratory tract infections; for people aged 75 years and older because of its potential to reduce mortality risk; for pregnant women due to its potential to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for individuals with high-risk prediabetes due to its potential to reduce the progression to diabetes.
Since the vitamin D doses in the included clinical trials varied significantly and many trial participants were allowed to continue their vitamin D-containing supplements, the optimal doses for empirical vitamin D supplementation remain unclear for the populations considered.
For non-pregnant individuals over 50 years old who require vitamin D, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel advises against using empirical vitamin D supplementation beyond the current DRIs to reduce the risk of disease in healthy adults under 75.
No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, including those with obesity or darker skin tone, and there was no clear evidence defining the optimal 25(OH)D level required for disease prevention in the populations considered. Thus, the panel suggests against routine 25(OH)D testing in all considered populations. The panel judged that in most situations, empirical vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and healthcare professionals, and does not negatively impact health equity.
In conclusion, the study suggests empirical vitamin D supplementation for children and adolescents aged 1 to 18 years, adults over 75 years old, pregnant women, and for those with high-risk prediabetes.
Given the scarcity of natural food sources rich in vitamin D, empirical supplementation can be achieved through a combination of fortified foods and vitamin D-containing supplements.
Based on the absence of supportive clinical trial evidence, the study advises against routine 25(OH)D testing in the absence of established indications.
These recommendations are not intended to replace the current DRIs for vitamin D, nor do they apply to individuals with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine the optimal 25(OH)D levels for specific health benefits.
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Source: Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M, Lips P, Mitchell DM, Murad MH, Powers S, Rao SD, Scragg R, Tayek JA, Valent AM, Walsh JME, McCartney CR. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024 Jul 12;109(8):1907-1947. doi: 10.1210/clinem/dgae290. PMID: 38828931.
