Vitamin D for the Prevention of Disease Guideline Resources

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline
JCEM | August 2024 (online June 2024)

Marie B. Demay (Chair), Anastassios G. Pittas (Co-Chair), 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

The 2024 guideline on vitamin D for the prevention of disease:

Essential Points

• Numerous studies demonstrate an association between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. This has led to widespread supplementation with vitamin D supplementation and increased laboratory testing for 25(OH)D in the general population.
• The benefit-risk ratio of this increase in vitamin D supplementation is not clear, and the optimal vitamin D intake and serum 25(OH)D concentrations for disease prevention remain uncertain.
• This guideline offers clinical guidelines for the use of vitamin D to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing.

List of Recommendation

Question 1. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used for children and adolescents (ages 1-18 years)?

Recommendation 1

In children and adolescents ages 1-18 years, we suggest empiric vitamin D supplementation to prevent nutritional rickets and potentially lower the risk of respiratory tract infections. (2 | ⊕⊕OO)

• Empiric vitamin D may include daily intake of fortified foods, vitamin formulations that contain vitamin D and/or daily intake of a vitamin D supplement (pill or drops).
• In the clinical trials included in the SR, with respect to respiratory tract infections in children, vitamin D doses ranged from 300 to 2000 IU (7.5 to 50 μg) daily equivalent. The estimated weighted average was approximately 1200 IU (30 μg) per day.

Question 2. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used for nonpregnant adults <50 years of age?

Recommendation 2
In the general adult population younger than age 50 years, we suggest against empiric vitamin D supplementation. (2 | ⊕◯◯◯)

• This recommendation relates to empiric vitamin D supplementation that exceeds the DRIs established by the IOM. Adults in this age group should follow the Recommended Daily Allowance established by the IOM (600 IU [15 µg] daily).

Question 3. Should vitamin D supplementation vs no vitamin D supplementation be used for nonpregnant adults <50 years of age only when 25(OH)D levels are below a threshold?

Recommendation 3

In the general adult population younger than age 50 years, we suggest against routine 25(OH)D testing. (2 | ⊕OOO)

• In this population, 25(OH)D levels that provide outcome-specific benefits have not been established in clinical trials.
• The panel suggests against (a) routine screening for a 25(OH)D level to guide decision-making (i.e., vitamin D vs no vitamin D) and (b) routine follow-up testing for 25(OH)D level to guide vitamin D dosing.
• This recommendation relates to generally healthy adults who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia).

Question 4. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used for adults aged 50-74 years?

Recommendation 4

In the general population ages 50 to 74 years, we suggest against routine vitamin D supplementation. (2 | ⊕⊕⊕O)

• This recommendation relates to empiric vitamin D supplementation that exceeds the DRIs established by the IOM. Adults in this age group should follow the Recommended Daily Allowance established by the IOM (600 IU [15 μg] daily for those aged 50 to 70 years; 800 IU [20 μg] daily for those older than 70 years).

Question 5. Should vitamin D supplementation vs no vitamin D supplementation be used for adults aged 50-74 years only when 25(OH)D levels are below a threshold?

Recommendation 5

In the general population ages 50 to 74 years, we suggest against routine 25(OH)D testing. (2 | ⊕OOO)

• In this population, 25(OH)D levels that provide outcome-specific benefits have not been established in clinical trials.
• The panel suggests against (a) routine screening for a 25(OH)D level to guide decision-making (i.e., vitamin D vs no vitamin D) and (b) routine follow-up testing for 25(OH)D level to guide vitamin D dosing.
• This recommendation relates to generally healthy adults who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia).

Question 6. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used by adults ages >75 years?

Recommendation 6

In the general population ages 75 years and older, we suggest empiric vitamin D supplementation because of the potential to lower the risk of mortality. (2 | ⊕⊕⊕O)

• Empiric vitamin D may include daily intake of fortified foods, vitamin formulations that contain vitamin D and/or daily intake of a vitamin D supplement.
• For empiric supplementation, daily, lower-dose vitamin D is preferred over non-daily, higher doses. 
• In the clinical trials included in the SR that reported on the mortality outcome, vitamin D dose ranged from 400 to 3333 IU [10 to 83 μg] daily equivalent. The estimated weighted average was average was approximately 900 IU (23 μg) daily. Participants in many trials were allowed to remain on their routine supplements, including up to 800 IU (20 μg) of vitamin D daily.

Question 7. Should vitamin D supplementation vs no vitamin D supplementation be used by adults ages >75 years only when 25(OH)D levels are below a threshold?

Recommendation 7

In the general population ages 75 years and older, we suggest against routine testing for 25(OH)D levels. (2 | ⊕OOO)

• In this population, 25(OH)D thresholds that provide outcome-specific benefits have not been established in clinical trials.
• The panel suggests against (a) routine screening for a 25(OH)D level to guide decision-making (i.e., vitamin D vs no vitamin D) and (b) routine follow-up testing for 25(OH)D level to guide vitamin D dosing.
• This recommendation relates to generally healthy adults who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia).

Question 8. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used during pregnancy?

Recommendation 8

We suggest empiric vitamin D supplementation during pregnancy, given its potential to lower risk of preeclampsia, intra-uterine mortality, preterm birth, small for gestational age birth, and neonatal mortality. (2 | ⊕⊕OO)

• This recommendation is based on evidence from trials conducted in healthy individuals during pregnancy. 
• Empiric vitamin D may include daily intake of fortified foods, prenatal vitamin formulations that contain vitamin D, and/or a vitamin D supplement (pills or drops).
• In the clinical trials included in the SR, the vitamin D doses ranged from 600 to 5000 IU (15 -125 μg) daily equivalent, usually provided daily or weekly. The estimated weighted average was approximately 2500 IU (63 μg) per day.

Question 9. Should vitamin D supplementation vs no vitamin D supplementation be used during pregnancy only when 25(OH)D levels are below a threshold?

Recommendation 9

During pregnancy, we suggest against routine 25(OH)D testing. (2 | ⊕OOO)

• In this population, 25(OH)D levels that provide pregnancy outcome-specific benefits have not been established in clinical trials.
• The panel suggests against (a) routine screening for a 25(OH)D level to guide decision-making (ie, vitamin D vs no vitamin D) and (b) routine follow-up testing for 25(OH)D level to guide vitamin D dosing.
• This recommendation relates to generally healthy pregnant individuals who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia). 

Question 10. Should empiric vitamin D supplementation vs no empiric vitamin D supplementation be used for adults with prediabetes (by glycemic criteria)?

Recommendation 10

For adults with high-risk prediabetes, in addition to lifestyle modification, we suggest empiric vitamin D supplementation to reduce the risk of progression to diabetes. (2 | ⊕⊕⊕O)

• Lifestyle modification must be a routine management component for adults with prediabetes.
• The clinical trials informing this recommendation primarily related to adults with high-risk prediabetes, identified as meeting two or three American Diabetes Association glycemia criteria (fasting glucose, HbA1c, 2-hour glucose after a 75-gram oral glucose challenge) for prediabetes and those with impaired glucose tolerance.
• In the clinical trials included in the SR, the vitamin D doses ranged from 842 to 7543 IU (21 to 189 μg) daily equivalent. The estimated weighted average was approximately 3500 IU (88 μg) per day. Participants in some trials were allowed to remain on their routine supplements, including up to 1000 IU (25 μg) of vitamin D daily.

Question 11. Should a daily, lower-dose vitamin D vs. non-daily (i.e., intermittent), higher-dose vitamin D be used for nonpregnant people for whom vitamin D treatment is indicated?

Recommendation 11

In adults ages 50 years and older who have indications for vitamin D supplementation or treatment, we suggest daily, lower-dose vitamin D instead of non-daily, higher-dose vitamin D. (2 | ⊕⊕OO)

• The panel did not identify evidence related to individuals younger than age 50 years.

Question 12. Should screening with a 25(OH)D test (with vitamin D supplementation/treatment only if below a threshold) vs no screening with a 25(OH)D test be used for healthy adults?

Recommendation 12

In healthy adults, we suggest against routine screening for 25(OH)D levels. (2 | ⊕OOO)

• In healthy adults, 25(OH)D levels that provide outcome-specific benefits have not been established in clinical trials.
• This recommendation relates to adults who do not otherwise have established indications for testing with 25(OH)D levels (e.g., hypocalcemia).

Question 13. Should screening with a 25(OH)D test (with vitamin D supplementation/treatment only if below a threshold) vs no screening with a 25(OH)D test be used for adults with dark complexion?

Recommendation 13

In adults with dark complexion, we suggest against routine screening for 25(OH)D levels. (2 | ⊕OOO)

• This recommendation relates to generally healthy adults with dark complexion who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia).
• The panel did not identify any clinical trials that related clinical outcomes to skin complexion per se. A secondary analysis did not clearly suggest net benefit with vitamin D in those who self-identify as Black. The panel recognized that self-identified race is an inaccurate and otherwise problematic proxy for dark complexion.

Question 14. Should screening with a 25(OH)D test (with vitamin D supplementation/treatment only if below a threshold) vs no screening with a 25(OH)D test be used for adults with obesity?

Recommendation 14

In adults with obesity, we suggest against routine screening for 25(OH)D levels. (2 | ⊕OOO)

• In adults with obesity, 25(OH)D thresholds that provide outcome-specific benefits have not been established in clinical trials.
• This recommendation relates to generally healthy adults with obesity who do not otherwise have established indications for 25(OH)D testing (e.g., hypocalcemia).

https://www.endocrine.org/clinical-practice-guidelines/vitamin-d-for-prevention-of-disease

https://www.panmerseyapc.nhs.uk/media/2146/vitamind_adult.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC9920487