by Lindsey A Hohlt, Doctor of Pharmacy Candidate
In June of 2024, the Endocrine Society published new clinical practice guidelines for the testing and supplementation of Vitamin D for the prevention of disease.1 Levels of vitamin D are routinely measured in the ambulatory setting due to the association of low vitamin D status with diseases such as osteoporosis.2 However, these new guidelines do not recommend routine screening in healthy populations with the exception of those with an established indication. This differs from the Endocrine Society’s previous guidelines, which recommended screening for vitamin D deficiency in individuals at risk, such as those who are pregnant, those who have a dark complexion, and those who are obese.3 The guideline panel also provides recommendations for supplementation, which includes more patient groups than in previous guidelines, including patients aged 1 to 18 years old, patients aged 75 and above, patients who are pregnant, and surprisingly, patients who are at risk for type 2 diabetes. The updated guidelines provide a new direction for health practitioners.
Screening
The updated guidelines conclude that routine screening for healthy adults is not cost effective, despite the widespread use of screening tests in recent years. The authors noted that there is not an appropriate threshold for which levels would indicate the patients’ vitamin D stores are “low”. Further, they stated that while there is an increased prevalence of low vitamin D in certain communities (e.g., people with dark complexions, people who are obese), the benefit of the screening is not worth the costs. There is also a lack of clinical trial evidence that shows any benefit to screening vitamin D concentrations in healthy adults. However, in special populations, such as those who have malabsorption issues (e.g., cystic fibrosis) or increased vitamin D loss (e.g., nephrotic syndrome, hypocalcemia), may benefit from screening.
Supplementation Guidelines
The guidelines discuss patient populations that benefit from empiric vitamin D supplementation. Empiric supplementation involves doses that exceed the Dietary Reference Intakes (DRI) and without testing vitamin D concentrations. Due to the diversity of vitamin D dosages used in clinical trials and the amount of vitamin D contained in available supplements, a standard recommended dose was not defined. However, the authors recommend that nonpregnant people older than 50 who may benefit from supplementation use daily “lower” doses rather than “higher” doses taken intermittently. Empiric vitamin D supplementation is recommended in the following groups:
- Children aged 1 to 18 years
- Adults aged 75+
- Woman who are pregnant
- Patients who have prediabetes
Vitamin D Supplementation and Prediabetes
Interestingly, the guidelines provided recommendations for those with prediabetes to supplement with vitamin D to prevent the progression to diabetes. The authors examined clinical trials involving 5,316 participants with prediabetes conducted in six countries (4 in India, 1 in Iran, 1 in Greece, 1 in Norway, 1 in Japan, and 3 in the US) to support this recommendation. The trials used varying daily dosages of vitamin D [842-7543 IU (21-189 μg); weighted average of 3,500 IU (88 μg)]. The summarized results showed that vitamin D supplementation reduced the risk of progressing to type 2 diabetes by 10% (RR 0.90, 95% CI 0.81-1.00). This translates to 24 fewer cases of diabetes progression per 1,000 patients with prediabetes. They also analyzed trials that examined the effects of vitamin D on HbA1c and glucose levels, both fasting and postprandial. The majority of trials used cholecalciferol or ergocalciferol vitamin D analogs. However, one of the larger trials examined used eldecalcitol, an active vitamin D analog. The panel justified empiric supplementation by stating “…that the anticipated desirable effects of vitamin D for diabetes prevention are likely moderate, while the anticipated undesirable effects are likely trivial.” They also examined the frequency of adverse effects in patients who had vitamin D supplementation. Adverse effects associated with vitamin D supplementation in these studies occurred about 0.4% more frequently in those taking a supplement compared to those who were not. While the risk reduction for diabetes progression is small, there is minimal harm from empiric treatment of Vitamin D, especially if there is a chance that a patient may benefit from the supplementation.
Prediabetes Evidence Summary
| Type of Study | Number of Studies | Vitamin D Supplementation | No Supplementation | Relative (95% CI) | Absolute (95% CI) |
| Prediabetes Progressing to T2DM | 10 | 438/2039 (21.5%) progressed to diabetes | 487/2021 (24.1%) progressed to diabetes | RR 0.90 (0.81 to 1.00) | 24 fewer per 1,000 (46 to 0) |
| Adverse Events (nephrolithiasis, hypercalcemia, renal dysfunction) | 2 | 30/1535 (2.0%) experienced adverse effects | 25/1536 (1.6%) experienced adverse effects | RR 1.20 (0.71 to 2.03) | 3 more per 1,000 (5 to 17) |
Key Take-Aways
In summary, this guideline provides new and important information for practitioners to consider for patients who may benefit from vitamin D supplementation. The panel recommends against performing vitamin D screening tests in healthy individuals due to the lack of evidence that screening is cost-effective. There are several clearly defined populations that might benefit from supplementation. However, the authors acknowledged the limitations to these recommendations based on the lack of high-quality clinical trial evidence. Further, many participants in the clinical trials had external vitamin D exposure from dietary sources and the sun. Moreover, the long-term effects of empiric vitamin D supplementation are unclear due to insufficient trial durations. Lastly, a majority of the trials enrolled patients who were of non-Hispanic white European ancestry, which limits the generalizability of these recommendations.
Summary of Recommendations
| Patient Population | Screening Recommendation | Supplementation Recommendation |
| Pregnancy | No | Yes |
| Ages 1-18 | No | Yes |
| Ages 75+ | No | Yes |
| Prediabetes | No | Yes |
| Dark Complexion | No | No |
| Obesity | No | No |
| Healthy Adults | No | No |
References
- Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M, Lips P, Mitchell DM, Murad MH, Powers S, Rao SD. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2024;109(8):1907-47.
- Heaney RP. Vitamin D in health and disease. Clinical Journal of the American Society of Nephrology. 2008;3(5):1535-41.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of Vitamin D deficiency: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology & metabolism. 2011;96(7):1911-30.
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