The Vitamin D Dilemma: Comparing 2011 & 2024 Vitamin D Guidelines

Molly Malecha, PharmD; Hennepin Healthcare

Background: Vitamin D is naturally synthesized by the skin following UV-B sun exposure, and can be consumed through a diet rich in fish, dairy, and fortified grains. Vitamin D is suggested to have an array of effects such as inhibiting angiogenesis and stimulating insulin production. However, vitamin D is best known for its role in facilitating calcium absorption and maintaining bone health. Accordingly, vitamin D deficiency is associated with numerous adverse outcomes: osteomalacia, respiratory illness, adverse pregnancy outcomes and development of chronic disease. The latest National Health and Nutrition Examination Survey published in 2022 estimated that 65.5% of Americans are deficient in vitamin D, which has resulted in a recent push for screening and empiric supplementation.

Evidence: The 2011 Endocrine Society Clinical Practice Guideline concentrated on the evaluation, treatment and prevention of vitamin D deficiency. The 2024 Endocrine Society Clinical Practice Guideline, however, focuses on vitamin D’s utility in preventing disease in “generally healthy” individuals. Both sets of guidelines leveraged a task force of Endocrinology experts to conduct systematic reviews of evidence to inform their recommendations. Large, randomized controlled trials were prioritized, however studies of this quality were difficult to find as vitamin D exposure and supplementation is so ubiquitous. As a result, most evidence was considered of low or very low certainty, ultimately making most recommendations “conditional” in both guidelines. This signifies that “desirable consequences probably outweigh undesirable consequences in most settings (or vice versa)”. 

Discussion: The 2011 guideline suggested serum 25-hydroxyvitamin D levels that would define deficiency (< 20 ng/mL), insufficiency (21-29 ng/mL) and sufficiency (30-100 ng/mL). This guideline also established recommended dietary intake (RDI) for different age groups, as well as appropriate doses for treatment of deficiency (see table below). This guideline specifically addresses populations that may have different requirements including pregnant women, individuals with obesity and/or malabsorption syndrome, and individuals on medications that would enhance vitamin D catabolism. Furthermore, this guideline endorsed that either once daily or once weekly dosing was appropriate for vitamin D treatment and prevention.

The 2024 guideline both challenges and builds upon information provided in the 2011 guidelines. The Endocrine Society no longer endorses the target 25-hydroxyvitamin D level as 30 ng/mL, nor does it endorse the specific levels that define sufficiency, insufficiency or deficiency. Regarding RDI and treatment to correct deficiency, this guideline defers to the amounts/doses published in the 2011 guideline. Recommendations unique to the 2024 guideline are summarized in the table below. This includes support only for empiric supplementation beyond the RDI for ages 1-18 and > 75, and those with pregnancy or high-risk prediabetes. These guidelines also suggest daily, lower-dose vitamin D instead of nondaily, higher-dose vitamin D for those age > 50 indicated for supplementation or treatment. Due to the range of doses used in trials, however, this guideline does not provide a recommended amount of supplementation for any group that is indicated. Routine serum 25-hydroxyvitaminD screening for all age and risk groups specified was also recommended against, largely due to unclear cutoffs for deficiency vs. sufficiency. Of note, the 2024 guidelines solely addressed “generally healthy” adults, and excluded those who may have altered vitamin D metabolism due to malabsorption, renal or hepatic deficiencies. 

Clinical Impact: While it is important to meet the vitamin D RDI, most healthy individuals do not have an indication for screening or empiric supplementation per the 2024 Endocrine Society guideline. These recommendations challenge the notion that vitamin D supplementation is beneficial to all individuals, which may limit use in the general population. For those that do have an indication for screening and supplementation, however, these guidelines fail to recommend specific doses for supplementation, or thresholds to evaluate vitamin D levels. Additionally, the 2024 guideline does not address those who are not “generally healthy,” so it cannot be applied to individuals with altered vitamin D metabolism due to renal or hepatic dysfunction, malabsorption or certain cancers. This lack of specificity will require providers to use their own discretion when evaluating vitamin D levels and dosing for supplementation. 

References:

1. Sizar O, Khare S, Goyal A, Givler A. Vitamin D deficiency. NCBI StatPearls. Published July 17, 2023. Accessed August 7, 2024. https://www.ncbi.nlm.nih.gov/books/NBK532266/
2. Cui A, Xiao P, Ma Y, Fan Z, et. al. Prevalence, trend, and predictor analyses of vitamin D deficiency in the US population, 2001-2018. Front Nutr. 2022; 9: 965376. doi: 10.3389/fnut.2022.965376. 
3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. Journal Clin Endocrinol & Metab. 2011; 96(7):1911–1930. https://doi.org/10.1210/jc.2011-0385
4. Demay MB, Pittas AG, Bikle DB, Diab DL, et al. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. Journal Clin Endocrinol & Metab. 2024; 109(8):1907–1947. https://doi.org/10.1210/clinem/dgae290