Clinical guidelines for empirical vitamin D supplementation: recommendations and preventive health benefits
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.
While a clear causal link between serum 25(OH)D concentrations and many 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 risk-benefit ratio of this increased use of vitamin D is unclear, and the optimal intake of vitamin D and the role of 25(OH)D testing in disease prevention remain uncertain.
Developing clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to reduce disease risk 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 reduce disease risk.
The panel prioritized placebo-controlled randomized 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 life, as well as in selected conditions (pregnancy and prediabetes).
The panel defined “empirical supplementation” as intake of vitamin D that (a) exceeds recommended intake values (Dietary Reference Intakes [DRI]) and (b) is implemented without 25(OH)D testing. Systematic reviews queried electronic databases for publications related to these 14 clinical questions.
GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resource requirements, acceptability and feasibility, and the impact on health equity of the proposed recommendations.
The process for developing these clinical guidelines did not use a risk assessment framework and was not designed to replace current recommended intake values for vitamin D.
The panel recommends empirical vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and for its potential to reduce the risk of respiratory tract infections.
For those aged 75 years and older, vitamin D supplementation is recommended for its potential to reduce mortality risk.
In pregnant women, vitamin D is recommended for its potential to reduce the risk of preeclampsia, intrauterine mortality, preterm birth, small for gestational age neonates, and neonatal mortality.
Finally, for individuals with high-risk prediabetes, vitamin D supplementation is suggested for its potential to reduce progression to diabetes.
Since vitamin D doses varied considerably in included clinical trials and many participants were allowed to continue their vitamin D-containing supplements, optimal doses for empirical vitamin D supplementation remain unclear for the populations considered.
For non-pregnant individuals over 50 years of age with indications for vitamin D, the panel suggests supplementation through daily administration of vitamin D rather than intermittent use of high doses. The panel recommends against empirical vitamin D supplementation beyond current recommended intake values to reduce disease risk in healthy adults under 75 years of age.
No evidence from clinical trials supported routine screening for 25(OH)D in the general population, nor in those with obesity or dark skin tones, and no clear findings defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; therefore, the panel suggests against routine testing for 25(OH)D in all considered populations.
The panel judged that, in most situations, empirical vitamin D supplementation is economical, feasible, acceptable to both healthy individuals and healthcare professionals and has no adverse effects on health equity.
These recommendations are not intended to replace current recommended intake values 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 optimal 25(OH)D levels for specific health benefits.
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Source : Marie B Demay, Anastassios G Pittas, Daniel D Bikle, Dima L Diab, Mairead E Kiely, Marise Lazaretti-Castro, Paul Lips, Deborah M Mitchell, M Hassan Murad, Shelley Powers, Sudhaker D Rao, Robert Scragg, John A Tayek, Amy M Valent, Judith M E Walsh, Christopher R McCartney, Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae290, https://doi.org/10.1210/clinem/dgae290
