The ABCs of Vitamin D Supplements: Exploring Their Health Benefits and Proper Use

According to the National Institutes of Health Office of Dietary Supplements (NIHODS), vitamin D, also known as calciferol, is a fat-soluble nutrient naturally found in a limited number of foods, such as egg yolks, beef liver, and fatty fish. Vitamin D is also added to other foods, such as milk and breakfast cereals, and is widely available in dietary supplements.^1,2

Vitamin D exists in 2 forms^1,2:

1. Cholecalciferol (vitamin D₃) is the naturally occurring form of vitamin D that is synthesized in the skin from endogenous or dietary cholesterol upon exposure to ultraviolet radiation (sunlight).
2. Ergocalciferol (vitamin D₂) is a plant-derived form used as a food additive.

The 2 forms only differ chemically in their side-chain structures, and both are well absorbed in the small intestine. The NIHODS notes that absorption occurs by simple passive diffusion and by a mechanism that involves intestinal membrane carrier proteins.^1,2

Research has established that vitamin D plays a critical role in calcium absorption and bone health.^1,2 It facilitates intestinal uptake of calcium and phosphate, helping maintain serum concentrations necessary for bone mineralization and preventing hypocalcemic tetany, which is an involuntary contraction of muscles, causing cramps and spasms.^1,2 Vitamin D is essential for bone growth and remodeling through its regulation of osteoblast and osteoclast activity, and research indicates that deficiency can manifest in skeletal disorders such as rickets in children and osteomalacia in adults, whereas adequate levels, especially when combined with calcium, can diminish the risk of osteoporosis in older adults.^1,2

Beyond its skeletal functions, research has shown that vitamin D contributes to immune support, maintenance of neuromuscular function, inflammation control, cell growth modulation, and blood pressure regulation. It may also decrease the risk of multiple sclerosis and depression and improve glucose metabolism in individuals with diabetes, thus highlighting its multifaceted roles in overall health and well-being. However, results have been variable and additional research is warranted.^1,2

Certain patient populations are more likely than others to have inadequate vitamin D levels. These include older adults, individuals with gastrointestinal disorders that impair absorption (eg, chronic pancreatitis), those with insufficient sun exposure, people with dark skin pigmentation, individuals with hereditary disorders affecting vitamin D metabolism, those with conditions that limit fat absorption, individuals with obesity or a history of gastric bypass, and patients receiving long-term antiseizure therapy (eg, phenytoin or carbamazepine).^1,2

Vitamin D Supplements

According to data from the National Health and Nutrition Examination Survey, most people in the United States consume less than the recommended amounts of vitamin D.¹ The CDC indicates that in 2023, approximately 18.5% of US adults reported taking vitamin D supplements. Despite this, nearly two-thirds of Americans have suboptimal vitamin D levels, with an estimated 2.6% having severe deficiency and 22% with moderate deficiency. These figures highlight a significant gap between supplement use and vitamin D sufficiency across the population.³

Several vitamin D supplements are available as single-entity products. Some products contain a combination of vitamin D and calcium, and vitamin D is typically found in multivitamin supplement products available in various strengths and dosage forms, including capsules, soft gels, tablets, liquids, gummies, and sublingual tablets, to meet the specific needs of various patient populations. Most OTC vitamin D supplements contain D₃.

Recent News and Clinical Data

In 2025 study findings published in Medical Sciences, researchers aimed to examine the correlation between serum vitamin D levels and the presence of long COVID symptoms. Results revealed that individuals with lower vitamin D levels were more likely to experience persistent post–COVID-19 signs and symptoms, suggesting a potential role for vitamin D in mitigating the risk and severity of long COVID symptoms.⁴

In study findings published in Nutrition Reviews, researchers assessed the impact of vitamin D₂ supplementation on serum 25(OH)D₃ concentrations by analyzing data from randomized controlled trials. Researchers discovered that vitamin D₂ supplementation was associated with a significant reduction in 25(OH)D₃ levels, often lower than those observed in control groups not receiving vitamin D₂.⁵ The findings suggest that vitamin D₃ supplementation may be more beneficial for patients, although personal preferences and considerations should be taken into account.⁵

Study findings published in The American Journal of Clinical Nutrition presented findings from the randomized, double-blind, placebo-controlled VITAL trial (NCT01169259). Results revealed that vitamin D supplementation helps maintain telomeres, protective caps at the ends of chromosomes that shorten during aging and are correlated with the development of certain diseases. The researchers indicated that compared with placebo, vitamin D₃ supplementation significantly reduced telomere shortening over 4 years, preventing the equivalent of nearly 3 years of aging. However, ω-3 fatty acid supplementation had no significant effect on telomere length throughout follow-up.⁶

Findings of a meta-analysis published in Diabetology & Metabolic Syndrome found that vitamin D supplementation significantly improves cardiometabolic markers, including blood pressure, cholesterol, insulin sensitivity, and blood glucose levels. The researchers indicated that the most significant benefits were observed in older adults, individuals with low baseline vitamin D, and non-Western populations, and these findings support the potential role of vitamin D in promoting cardiovascular and metabolic health.⁷

Conclusion

Pharmacists play a critical role in identifying patients at risk for vitamin D deficiency, contraindications, and potential drug-nutrient interactions. Because vitamin D supplements can interact with medications such as corticosteroids, anticonvulsants, and some diuretics, potentially affecting drug metabolism, calcium levels, or vitamin D absorption, patients should consult their health care provider before use.²

Before recommending supplementation, patients with suspected nutritional deficiencies should be referred to their primary physician for appropriate evaluation, additional treatment, and medical monitoring. During counseling, pharmacists should emphasize adherence to recommended dosages unless otherwise directed by a provider. Patients should be advised to check supplement labels to avoid excessive intake. Although rare, vitamin D toxicity can cause symptoms such as fatigue, nausea, dry mouth, and muscle pain and may lead to serious complications such as hypercalcemia, kidney stones, or renal failure.²

The current upper limit for vitamin D for adults and children 9 years or older is 4000 IU (100 μg), and patients should be encouraged to discuss their individual vitamin D needs with their health care provider before taking these supplements, because needs may vary based on age, health status, and lifestyle factors.^2,8 Patients with underlying health conditions or those taking medications that may interact with vitamin D should consult their provider before initiating supplementation.

REFERENCES

1. Vitamin D. National Institutes of Health Office of Dietary Supplements. Updated June 27, 2025. Accessed November 14, 2025. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

2. Bridgeman A, Rollins C. Essential and conditionally essential nutrients. In: Krinsky DL, Ferreri SP, Hemstreet B, et al, eds. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. 21st edition. American Pharmacists Association; 2024.

3. Mishra S, Gahche JJ, Ogden CL, Dimeler M, Potischman N, Ahluwalia N. Dietary Supplement Use in the United States: National Health and Nutrition Examination Survey, 2017–March 2020. CDC. April 18, 2023. Accessed November 14, 2025. https://www.cdc.gov/nchs/data/nhsr/nhsr183.pdf

4. Matangkha K, Punyahotara V, Rintra J, Sittiprapaporn P. Association between vitamin D levels and long COVID signs and symptoms. Med Sci (Basel). 2025;13(3):199. doi:10.3390/medsci13030199

5. Brown EIG, Darling AL, Robertson TM, et al. Effect of vitamin D2 supplementation on 25-hydroxyvitamin D3 status: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2025;nuaf166. doi:10.1093/nutrit/nuaf166

6. Zhu H, Manson JE, Cook NR, et al. Vitamin D₃ and marine ω-3 fatty acids supplementation and leukocyte telomere length: four-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial. Am J Clin Nutr. 2025;122(1):39-47. doi:10.1016/j.ajcnut.2025.05.003

7. Ge L, Gao S, Kia N, Wang Y, Hua L. Effect of vitamin D supplementation on body composition, lipid profile, and glycemic indices in patients with obesity-associated metabolic syndrome: a systematic review and meta-analysis. Diabetol Metab Syndr. 2025;17(1):287. doi:10.1186/s13098-025-01799-1

8. Overview of vitamin D. UpToDate. Updated August 12, 2025. Accessed November 14, 2025. https://www.uptodate.com/contents/overview-of-vitamin-d