OPTIMIZING VITAMIN D USE: EVIDENCE-INFORMED DECISIONS ACROSS THE CARE TEAM
Faculty:
L. Austin Fredrickson, MD, FACP
L. Austin Fredrickson is an Associate Professor of Internal Medicine at Northeast Ohio Medical University, where he serves as core faculty and teaches diagnostics, therapeutics, clinical skills, and health humanities. He is board-certified in general internal medicine and practices rural primary care.âŻ
Liz Fredrickson, PharmD, BCPS
Liz Fredrickson, PharmD, BCPS, is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy, where she is course director of the Parenteral Products and Basic Pharmaceutics Lab courses.
Kristina (Tia) Neu, RN
Kristina (Tia) Neu is a licensed Registered Nurse and author currently developing in-service training for healthcare professionals. She is a National Board-Certified Health & Wellness and Lifestyle Medicine Coach. Her work experience includes several areas of the healthcare profession, including psychiatric nursing, medical nursing, motivational health coaching, chronic case management, dental hygiene, cardiac technology, and surgical technology.
Pamela Sardo, PharmD, BS
Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pamâs career spans many years in retail, clinics, hospitals, long-term care, the Veterans Affairs system, and managed health care, with responsibilities across a broad range of therapeutic classes and disease states.
Abstract
Vitamin D is best known for its role in musculoskeletal health, but its use to prevent other health issues and diseases remains an area of evolving evidence. This continuing educational activity examines contemporary research on vitamin D supplementation, screening practices, and population-specific outcomes related to chronic disease prevention, aging, and metabolic health. Through an interprofessional lens, participants will explore practical implications for laboratory testing, supplementation strategies, dosing frequency, and patient counseling, with the goal of optimizing benefit while minimizing unnecessary testing, overtreatment, and supplement-related harm.
Accreditation Statements
In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation CouncilTM for Continuing Medical Education (ACCMEÂŽ), the Accreditation Council for Pharmacy Education (ACPEÂŽ), and the American Nurses Credentialing Center (ANCCÂŽ), to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credits for learning and change.
Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:
Pharmacists: JA4008424-0000-26-025-H01-P
Pharmacy Technicians: JA4008424-0000-26-025-H01-T
Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.
Credit Types:
IPCE Credits - 2 Credits
AAPA Category 1 Creditâ˘ď¸ - 2 Credits
AMA PRA Category 1 Creditâ˘ď¸ - 2 Credits
Pharmacy - 2 Credits
Type of Activity: Application
Media: Computer-Based Training (i.e., online courses)
Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Activity Pre-Test, Post-Test, and Activity Evaluation.
Release Date: March 10, 2026 Expiration Date: March 10, 2029
Target Audience: This educational activity is for Physicians, Physician Assistants, Pharmacists, and Pharmacy Technicians
How to Earn Credit: From March 10, 2026, through March 10, 2029, participants must:
Read the âlearning objectivesâ and âauthor and planning team disclosures;â
Take the âEducational Activity Pre-Test;â
Study the section entitled âEducational Activity;â and
Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
CME Credit: Credit for this course will be uploaded to CPE MonitorÂŽ for pharmacists. Physicians may receive AMA PRA Category 1 Creditâ˘ď¸ and use these credits toward Maintenance of Certification (MOC) requirements. Physician Assistants may earn AAPA Category 1 CME credit, reportable through PA Portfolio. All learners shall verify their individual licensing boardâs specific requirements and eligibility criteria.
Statement of Need
Clinical teams overuse vitamin D screening and empiric supplementation, and may aim for arbitrary serum targets or long-term use of high-dose Vitamin D regimens. This occurs despite guideline recommendations against routine testing and broad use of preventive supplementation. Healthcare professionals may also overestimate benefits for cardiovascular, metabolic, oncologic, and immune outcomes, which contributes to costly, low-value care, and possible manifestation of toxicity symptoms. Vulnerable populations, including patients with obesity, malabsorption, chronic kidney disease, or pregnancy, are not consistently managed. Optimal patient management includes an individualized approach to Vitamin D dosing and appropriate formulation selection. Interprofessional coordination is often informal, and teams may miss opportunities for collaborative discussion, medication reconciliation, deprescribing, and unified patient counseling. This educational activity aims to align interprofessional practice with current evidence, promote risk-based testing and supplementation, and strengthen team-based strategies to optimize vitamin D use while minimizing harm.
Learning Objectives:
Upon completion of this educational activity, physicians and physician assistants should be able to:
Recall current evidence regarding vitamin D supplementation for disease prevention and differentiate populations most likely to benefit from supplementation
Assess the clinical utility of serum vitamin D testing in preventive care settings and integrate evidence-based reasoning into decisions regarding screening and monitoring
Select appropriate supplementation strategies, including dose and frequency, based on patient-specific factors
Upon completion of this educational activity, pharmacists should be able to:
Recall evidence on vitamin D supplementation and apply it to patient counseling, product selection, and interprofessional recommendations
Differentiate dosing approaches and formulations of vitamin D and assess their appropriateness based on patient characteristics, safety considerations, and adherence factors
Counsel patients on appropriate indications for, administration of, and adverse effects related to Vitamin D supplementation
Upon completion of this educational activity, pharmacy technicians should be able to:
Identify common vitamin D products and formulations, including differences in strength, dosage form, and combination products
Identify potential safety concerns related to vitamin D supplements
Recall the roles of the healthcare team with regard to Vitamin D supplementation
Disclosures
The following individuals were involved in planning, developing, and/or authoring this activity: L. Austin Fredrickson, MD, FACP; Kristina (Tia) Neu, RN; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.
Š RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Educational Activity Pre-Test
A 50-year-old woman with obesity and limited sun exposure asks whether taking Vitamin D will prevent fractures. Which statement reflects current evidence for disease prevention?
Vitamin D plus calcium offers modest fracture risk reduction in select high-risk patients
Vitamin D prevents all-cause mortality and should be prescribed for all those aged 50+
Vitamin D prevents type 2 diabetes in all patients presenting with prediabetes
Vitamin D reduces peripheral lower extremity fracture risk by 20% after 3 months.
An interprofessional team is meeting to reduce fracture risk and is deciding whether to screen asymptomatic adults for Vitamin D deficiency. Which patient is likely appropriate for screening?
A 28-year-old pregnant woman with adequate prenatal care and normal dietary intake
A 32-year-old marathon runner undergoing many hours of outdoor training
A 70-year-old man in a nursing home with frequent falls, limited sun exposure, and a diagnosis of osteoporosis
A 25-year-old roofer asking for a Vitamin D test out of curiosity because his coworker fell off a ladder
Which supplementation strategy is most appropriate in advanced chronic kidney disease?
High-dose cholecalciferol
Active Vitamin D analogs with monitoring
Intermittent bolus dosing
Avoid Vitamin D entirely
Educational Activity
Optimizing Vitamin D Use: Evidence-Informed Decisions Across the Care Team
Introduction
Vitamin D is one of the most discussed and misunderstood nutrients within healthcare. Historically, vitamin D has been used primarily to prevent skeletal conditions such as rickets and osteomalacia.1 More recently, vitamin D has become a routine part of preventive care discussions for conditions ranging from osteoporosis and falls to cardiovascular disease, cancer, immune health, and metabolic disorders.1 This expanded interest has been driven by observational studies linking low vitamin D levels to numerous diseases, increased media coverage, and the availability of over-the-counter supplements.2,3
As a result, vitamin D supplementation and laboratory testing have increased dramatically in recent years.4 Some patients now take daily or high-dose vitamin D supplements, often without a clear indication, and care teams are frequently faced with decisions about when to test, how to interpret results, and what dosing strategies are truly based on evidence.4 Additionally, results of large, randomized trials have led to important questions about who benefits from supplementation and whether routine screening improves clinical outcomes.5
In everyday practice, health care team members, including physicians, physician assistants, pharmacists, and pharmacy technicians, play important roles in guiding appropriate vitamin D use. These include helping patients navigate supplement selection, determine dosing frequency, and discuss safety concerns and expected benefits. This continuing education activity will review contemporary research on vitamin D supplementation, screening practices, and population-specific outcomes related to disease treatment and prevention. Through an interprofessional lens, participants will review recommendations for laboratory testing, supplementation strategies, and patient counseling to optimize benefits while minimizing unnecessary testing, overtreatment, and harm related to supplements.
Vitamin D Physiology and Chemistry
Vitamin D is a fat-soluble prohormone that is absorbed in the small intestine alongside dietary fats, a process that depends on adequate bile acid secretion and intact pancreatic function.6 Following intestinal absorption or cutaneous synthesis, vitamin D undergoes first-pass hydroxylation in the liver to form 25-hydroxyvitamin D (25OHD), the primary circulating form and the most reliable marker of vitamin D status.6 This is then converted in the kidneys by 1-Îą-hydroxylase into the biologically active hormone, 1,25-dihydroxyvitamin D [1,25(OH)âD], which regulates calcium and phosphorus homeostasis through actions in the intestine, bone, kidney, and parathyroid glands.6 Conversion to the active metabolite may be impaired in patients with chronic kidney disease. As a result, serum 25(OH)D concentrations may not fully reflect vitamin D activity in certain populations, underscoring the need for individualized assessment and management.
Vitamin D exerts its biological effects through activation of the vitamin D receptor (VDR), which is widely expressed in skeletal and non-skeletal tissues, including bone, intestine, kidney, and immune cells.6,7 The most well-established physiological role of vitamin D is the promotion of intestinal calcium absorption and maintenance of skeletal integrity throughout the lifespan.8 The presence of VDRs in non-skeletal tissues has also expanded interest in potential roles for vitamin D in immune regulation, cellular differentiation, and inflammatory pathways.9
An understanding of vitamin D absorption and metabolism is particularly important when caring for patients with chronic kidney disease, malabsorptive disorders, or those receiving medications that interfere with vitamin D absorption or activation, such as anticonvulsants, glucocorticoids, and bile acid sequestrants.10 In these clinical contexts, standard supplementation strategies may be insufficient or inappropriate, and alternative dosing approaches or formulations may be required to achieve therapeutic goals.
Pause and Ponder: When recommending vitamin D supplementation, what is the balance between guideline-based dosing and individual patient factors such as baseline vitamin D status, comorbid conditions, medication use, and risk of over-supplementation? |
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Epidemiology
The definition of vitamin D deficiency (VDD) varies across professional organizations, reflecting differences in the outcomes used to establish threshold values (Table 1).11 As a result, estimates of vitamin D deficiency and insufficiency vary substantially depending on which criteria are applied.11
Table 1
Definitions of Vitamin D Deficiency11
| Organization | Vitamin D Deficiency (VDD) | Vitamin D Insufficiency (VDI) | Basis for Thresholds |
|---|---|---|---|
| Institute of Medicine (IOM) | Serum 25(OH)D < 30 nmol/L (< 12 ng/mL) | Serum 25(OH)D 30â50 nmol/L (12â20 ng/mL) | Population-level skeletal outcomes, including parathyroid hormone suppression, calcium absorption, and bone mineral density |
| Endocrine Society (ES) | Serum 25(OH)D < 50 nmol/L (< 20 ng/mL) | Serum 25(OH)D 50â75 nmol/L (20â30 ng/mL) | Clinical and physiological targets intended to optimize bone health and minimize fracture and fall risk |
Using these definitions, population-based studies in the United States (US) have found that while severe vitamin D deficiency is relatively uncommon, insufficiency is far more prevalent.11 Estimates suggest that approximately 2.6% of adults have serum 25(OH)D concentrations < 25 nmol/L, 22.0% have levels between 25â50 nmol/L, and 40.9% fall within the 50â75 nmol/L range.11
Several demographic, behavioral, and clinical factors are associated with lower serum vitamin D levels. These include younger adult age (18â44 years), female sex, higher body mass index, limited dietary vitamin D intake, and sun-avoidant behaviors such as routine sunscreen use, wearing protective clothing, or spending little time outdoors.11 Lower vitamin D levels are also more commonly observed among Mexican American and non-Hispanic Black populations, reflecting differences in skin pigmentation, sun exposure, dietary intake, and structural determinants of health.11
Trends over time have suggested mild improvements in moderate vitamin D deficiency, which may be driven by increased laboratory testing, higher recommended supplementation doses, greater public awareness, and expanded fortification of processed foods.11 However, the prevalence of severe vitamin D deficiency has remained relatively stable.11 This is likely due to the continued impact of malabsorption, chronic illness, and social and behavioral risk factors that are less responsive to population-level interventions.11
Vitamin D Guideline Updates
The 2024 Endocrine Society Vitamin D for the Prevention of Disease Guideline represents a shift away from viewing vitamin D as a broadly beneficial preventive therapy toward a more evidence-driven approach focused on select populations.12 Unlike prior guidance centered on identifying and correcting biochemical deficiencies, the updated guideline prioritizes clinical outcome data from placebo-controlled trials conducted in general, healthy adult populations.12
While the guideline continues the recommended dietary intakes (RDIs) and treatment dosing strategies established in 2011, it removes endorsed serum 25-hydroxyvitamin D targets, discourages routine population-based screening, and limits empiric supplementation beyond RDIs to specific age and risk groups.12 These changes challenge long-standing clinical practices that have centered on routine testing and dose escalation with the goal of obtaining predefined serum Vitamin D levels.
For care team members, the updated guidance emphasizes the thoughtful use of laboratory testing, the avoidance of intermittent high-dose or bolus supplementation in most patients, and clear patient counseling on the limited extra-skeletal benefits of vitamin D supplementation in otherwise healthy adults.
Table 2
Comparison of 2011 and 2024 Endocrine Society Guidelines12,13
| Domain | 2011 Guideline | 2024 Guideline | Practice Implications |
|---|---|---|---|
| Primary Focus | Evaluation, treatment, and prevention of vitamin D deficiency | Prevention of disease in generally healthy individuals | Shift from deficiency correction to prevention evidence |
| Target Population | General population plus high-risk groups (obesity, malabsorption, pregnancy, interacting meds) | Generally healthy adults only | The 2024 guidance is not applicable to many clinical patients |
| Definition of Deficiency | Deficiency: <20 ng/mL Insufficiency: 21â29 ng/mL Sufficiency: âĽ30 ng/mL | No endorsed cutoffs for deficiency, insufficiency, or sufficiency | Removes lab-based treatment targets |
| Serum 25-OH-D Targets | Target âĽ30 ng/mL | No target level recommended | Avoid âtreat-to-numberâ strategies |
| Screening Recommendations | Screening reasonable in at-risk populations | Routine screening was discouraged in all included groups | Supports risk-based testing only |
| RDI Reference | Established RDIs by age group | Defers to 2011 RDI values | RDIs unchanged |
| Treatment of Deficiency | Explicit treatment regimens (daily or weekly high-dose options) | Defers to the 2011 treatment doses | Treatment guidance unchanged |
| Empiric Supplementation (Beyond RDI) | Broadly supported in at-risk populations | Limited to select groups only | Major narrowing of the supplementation scope |
| Populations Supported for Empiric Supplementation | High-risk patients (obesity, malabsorption, pregnancy, interacting meds) | Ages 1â18, >75, pregnancy, high-risk prediabetes | Healthy adults are largely excluded |
| Supplementation Dose Guidance | Specific doses provided | No specific doses recommended | Requires clinician judgment |
| Evidence Threshold | Observational + limited RCTs | Large RCTs prioritized; evidence has low certainty | Explains conditional recommendations |
Vitamin D and Effects on Health
Available evidence suggests that vitamin D supplementation is most beneficial for preventing and treating deficiency, rather than for reducing the risk of chronic disease more broadly.13 From a clinical practice perspective, vitamin D supplementation should be approached as a targeted therapy for deficiency and bone health rather than a universal preventive intervention.13 Clinical decision-making should prioritize identifying patients at risk for deficiency, avoiding excessive dosing, and aligning with guideline-recommended thresholds.12,14 The relationship of Vitamin D and various health disorders is described in more detail below.
Vitamin D and Musculoskeletal Health
The role of vitamin D in preventing rickets and osteomalacia is well established, and daily supplementation with approximately 400 international units (IU) is typically sufficient to prevent these conditions in children.14 In adults, the skeletal benefits of vitamin D supplementation are more nuanced. Large trials have found that vitamin D alone does not reduce the risk of fractures or meaningfully improve bone mineral density in vitamin Dâreplete adults.15
Correction of severe vitamin D deficiency may slow bone loss and modestly improve bone density, especially in older adults.14 Combined calcium and vitamin D supplementation may also reduce fracture risk in high-risk populations with low dietary calcium intake. Notably, very high daily doses of vitamin D have been associated with adverse skeletal effects, which highlights the importance of avoiding excessive supplementation.14
Vitamin D deficiency is associated with muscle weakness and an increased risk of falls in older adults.14 While some early studies suggested that supplementation might reduce falls, more recent large trials have not confirmed a consistent benefit.14 High-dose or intermittent bolus vitamin D regimens may increase fall risk. In general, routine vitamin D supplementation for fall prevention is not supported in vitamin Dâreplete individuals; however, correction of VDD remains appropriate in older adults at risk.14
Vitamin D and Cardiovascular Health
In observational studies, low serum vitamin D concentrations have been associated with an increased risk of cardiovascular disease, including hypertension, ischemic heart disease, heart failure, and stroke.14 However, observational findings may be confounded by lifestyle factors, comorbid illness, and socioeconomic status.14
Large randomized controlled trials, including the VIDA trial, have not demonstrated a reduction in major cardiovascular events or cardiovascular mortality with vitamin D supplementation in predominantly vitamin Dâreplete adults.14 Similarly, Mendelian randomization studies, which assess lifelong genetically determined differences in vitamin D status, have not supported a causal relationship between serum 25(OH)D levels and cardiovascular disease risk.14 Together, current high-quality evidence does not support the use of vitamin D supplementation for the primary or secondary prevention of cardiovascular disease in the general adult population.
Vitamin D and Metabolic Health (Type 2 Diabetes)
Observational studies previously suggested an association between low vitamin D status and an increased risk of type 2 diabetes mellitus (T2DM). 14More recent randomized trials, however, indicate that vitamin D supplementation does not meaningfully reduce progression from prediabetes to T2DM in the overall population.14 In the D2d trial, supplementation produced only a nonsignificant trend toward risk reduction.16 Vitamin D supplementation should not be routinely recommended for diabetes prevention; however, correcting deficiencies may have a modest benefit in select patients.
Vitamin D and Cancer
Experimental and observational data have linked vitamin D to cell cycle regulation and cancer biology, suggesting that supplementation may reduce cancer incidence and improve outcomes.14 Large, randomized trials have not shown a reduction in overall cancer incidence with vitamin D supplementation.14 However, some analyses suggest a modest reduction in cancer mortality, and there may be a delayed effect on disease progression.14 While a small protective effect on cancer mortality cannot be excluded, current evidence does not justify vitamin D supplementation for cancer prevention in vitamin Dâdeficient adults.14
Vitamin D and Immune / Respiratory Health
Vitamin D supports immune regulation, and meta-analyses of randomized trials suggest that supplementation may modestly reduce the risk of acute respiratory infections, particularly among individuals with severe vitamin D deficiency, when administered daily or weekly.14 Evidence for benefit in chronic lung disease, such as asthma or COPD, is inconsistent and appears limited to select subgroups.14
Data regarding associations between vitamin D and COVID-19 remain inconclusive.14 Observational studies suggest an association between low vitamin D levels and worse outcomes, but randomized studies have not demonstrated a clear benefit from supplementation.14
Vitamin D and Autoimmune Disease
Among autoimmune conditions, the strongest evidence for a causal role of vitamin D deficiency exists for multiple sclerosis (MS).14 Studies have demonstrated that genetically lower vitamin D levels are associated with increased MS risk.14 For other autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes, evidence from causal inference studies does not support a meaningful protective role for vitamin D supplementation.14
Special Populations
Obesity
Patients with obesity frequently exhibit lower circulating 25-hydroxyvitamin D concentrations despite comparable or higher vitamin D intake.17 This phenomenon is primarily related to sequestration of vitamin D within adipose tissue, reduced bioavailability, and delayed release into the circulation.17 As a result, standard supplementation with cholecalciferol may produce smaller or slower increases in serum 25(OH)D levels, and laboratory values may underestimate functional vitamin D status.18
Calcifediol may offer advantages in this population due to its greater intestinal absorption, reduced reliance on hepatic conversion, and more predictable effect on circulating 25(OH)D concentrations.18 Primary care providers and healthcare team members should interpret vitamin D levels cautiously in patients with obesity and consider higher or alternative supplementation strategies when clinically indicated, rather than assuming nonadherence or treatment failure.19
Pregnancy and Lactation
Adequate vitamin D status during pregnancy and breastfeeding is important for maternal skeletal health and fetal and infant development.20 Vitamin D deficiency during pregnancy has been associated with adverse outcomes, including preeclampsia, gestational diabetes, preterm birth, and impaired fetal growth, although optimal serum thresholds remain debated.20
Standard prenatal vitamin D doses may be insufficient for women at high risk of deficiency. During lactation, maternal vitamin D status directly influences the vitamin D content of breast milk, which is typically inadequate to meet infant needs without supplementation. While high-dose maternal supplementation can increase breast milk vitamin D levels, direct infant supplementation remains the most widely recommended and practical strategy to prevent vitamin D deficiency.
Vitamin D Screening
A comprehensive systematic review of 31 clinical guidelines published between 2013 and 2024 found that no organization recommended population-wide screening due to a lack of demonstrated clinical benefit, substantial healthcare costs, and ongoing uncertainty regarding optimal serum 25-hydroxyvitamin D thresholds.22 This aligns with recommendations from major organizations, including the U.S. Preventive Services Task Force and the Endocrine Society, both of which advise against routine screening in asymptomatic adults without risk factors.4,14
In contrast, targeted screening may be appropriate for select, high-risk patient populations. Several guidelines support vitamin D testing in individuals with conditions associated with an increased risk of, or clinical consequences of, deficiency, including osteoporosis, recurrent fractures, malabsorptive gastrointestinal disorders, chronic kidney or liver disease, long-term glucocorticoid therapy, bariatric surgery, and limited sun exposure.4,14 Older adults (65â75 years old) may also be good candidates for selective screening, though recommended thresholds and testing strategies vary widely across guidelines.4,14 Table 3 details conditions affecting Vitamin D status.6
Pause and Ponder: In your experience, does clinical practice regarding vitamin D screening and supplementation align with current evidence? Are there patient populations where clinical practice may need to be refined? |
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Table 3
Conditions Affecting Vitamin D Status6
| Category | Examples | Mechanism Affecting Vitamin D Status |
|---|---|---|
| Reduced absorptive surface | Celiac disease, tropical sprue | Villous atrophy limits fat-soluble vitamin absorption |
| Inflammatory bowel disease | Crohnâs disease, ulcerative colitis | Chronic inflammation, bile salt malabsorption, dietary restriction |
| Bariatric surgery | Roux-en-Y gastric bypass, biliopancreatic diversion, sleeve gastrectomy | Reduced intestinal surface area and fat absorption |
| Chronic infectious diarrhea | Whipple disease, HIV enteropathy, parasitic infections | Prolonged nutrient malabsorption |
| Short bowel or radiation injury | Short bowel syndrome, radiation enteritis | Loss of functional absorptive capacity |
| Gastrointestinal malignancy | Intestinal lymphoma, Kaposi sarcoma | Disruption of mucosal integrity |
| Small intestinal dysbiosis* | Small bowel bacterial overgrowth | Altered bile acid metabolism |
| Pancreatic exocrine insufficiency | Chronic pancreatitis, cystic fibrosis | Impaired fat digestion |
| Disorders of bile acid metabolism | Cholestasis, advanced cirrhosis | Reduced micelle formation for fat-soluble vitamins |
*dysbiosis -imbalance in the gut microbiome
There is substantial variability in laboratory assay methods and reference ranges across published guidelines, which can complicate the interpretation of serum 25-hydroxyvitamin D results.23 These limitations reinforce the need for an individualized approach to testing rather than reflexive or routine screening.
Practice Point: Current guidelines favor risk-based screening over universal testing and emphasize laboratory evaluation and shared decision-making for patients with known risk factors or bone health concerns.14 |
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Sources of Vitamin D
Exposure to ultraviolet B (UV-B) radiation from sunlight is a major natural source of vitamin D. Factors such as season, latitude, time of day, skin pigmentation, age, sunscreen use, clothing coverage, and time spent outdoors can all significantly influence vitamin D production.24 Because of this variability, many individuals rely on dietary sources and supplementation to meet recommended intakes.24 Healthcare professionals play an important role in assessing patientsâ dietary intake, supplement use, and sun exposure during medication reconciliation and preventive care visits.
Clinical Pearl: Native vitamin D (cholecalciferol or calcifediol) supports physiologic regulation of vitamin D metabolism, whereas calcitriol bypasses regulatory controls and should be reserved for select indications.25 |
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Naturally occurring vitamin D is present in relatively few foods. Fatty fish and fish liver oils provide the highest amounts, while smaller quantities are found in egg yolks and beef liver.24 In the US, the majority of dietary vitamin D intake comes from fortified foods, including cowâs milk, plant-based milk alternatives, breakfast cereals, yogurt, and some orange juices (Table 4).24
Table 4
Food Sources of Vitamin D24
| Food | Serving Size | Approx. Vitamin D (IU) |
|---|---|---|
| Rainbow trout (fresh) | 3 oz cooked | ~645 IU (~108% DV) |
| Salmon (various) | 3 oz cooked | ~383â570 IU |
| Light tuna, canned | 3 oz | ~231 IU |
| Herring | 3 oz | ~182 IU |
| Sardines, canned | 3 oz | ~164 IU |
| Tilapia | 3 oz | ~127 IU |
| Flounder | 3 oz | ~118 IU |
| Fortified cowâs milk | 1 cup | ~100â120 IU |
| Fortified plant-based milks | 1 cup | ~100â144 IU |
| Fortified orange juice | 1 cup | ~100 IU |
| Fortified cereal | 1 serving | ~80 IU |
| Egg yolk (large) | 1 yolk | ~37â41 IU |
| UV-exposed mushrooms | ½ cup | ~110â136 IU (varies with UV exposure) |
| Cod liver oil | 1 tbsp | ~1,360 IU (very high) |
Dietary supplements are widely used to help individuals meet the recommended vitamin D intake, particularly those with limited sun exposure or at increased risk of deficiency (Table 5). When selecting a formulation, the healthcare team should consider patient-specific factors, including adherence, swallowing ability, gastrointestinal absorption, dosing accuracy, and concomitant calcium use. Pharmacists are uniquely positioned to guide formulation selection and dosing precision. This could include recommending liquid formulations for pediatric patients or those with difficulty swallowing. Prescribers should ensure supplementation aligns with a clear clinical indication rather than perceived general health benefit.
Table 5
Vitamin D Formulations25
| Type | Description | Notes on Use/Absorption |
|---|---|---|
| Vitamin Dâ (Ergocalciferol) | Plant-derived form of vitamin D | Absorbed in the gut; used in supplements and fortified foods; requires conversion to active metabolites similar to Dâ |
| Vitamin Dâ (Cholecalciferol) | Animal-derived form (also produced in skin with UV exposure) | Most common supplement form; generally considered more effective at raising and maintaining serum 25(OH)D levels than Dâ |
| Calcidiol (25-hydroxyvitamin D) | Pre-activated form of vitamin D | Less commonly used as a supplement; it directly reflects status in the circulation, but is not routinely used for general supplementation. |
| Combined Formulations (e.g., D + Calcium, Multivitamins) | Vitamin D is included with other nutrients | Often used to support bone health; useful when additional nutrients (e.g., calcium) are also needed. |
| Variable Delivery Formats | Capsules, softgels, tablets, liquids, chewables, gummies | Choice depends on patient preference, age, swallowing ability, and dosing needs; absorption may be enhanced with dietary fat |
Current Supplementation Recommendations
Differences between national dietary reference intakes and specialty society recommendations can create confusion for both healthcare professionals and patients. In practice, healthcare professionals should recognize that NIH/IOM recommendations (Table 6) are intended for the general population, while higher-dose recommendations are typically reserved for individuals with documented deficiencies or specific risk factors and should be paired with appropriate clinical monitoring.
Table 6
Vitamin D Intake Recommendations: NIH (IOM/NASEM) vs Endocrine Society4,14
| Population | NIH / IOM (NASEM) RDA* | Endocrine Society Recommendation | Key Distinction |
|---|---|---|---|
| Infants (0â12 months) | 400 IU/day | 400â1,000 IU/day | The Endocrine Society allows higher dosing in infants at risk for deficiency |
| Children 1â18 years | 600 IU/day | 600â1,000 IU/day | Higher doses suggested for children with risk factors |
| Adults 19â70 years | 600 IU/day | 1,500â2,000 IU/day | Endocrine Society targets higher serum levels |
| Adults >70 years | 800 IU/day | 1,500â2,000 IU/day | Higher intake recommended due to fracture/fall risk |
| Pregnant / Lactating | 600 IU/day | 1,500â2,000 IU/day | The Endocrine Society supports a higher intake to maintain sufficiency |
| Adults with obesity, malabsorption, or on interacting meds | Not specifically addressed | 2â3Ă higher than standard dose | NIH focuses on the general population; the Endocrine Society individualizes recommendations |
*NASEM - National Academies of Sciences, Engineering, and Medicine; NIH - National Institutes of Health; IOM - Institute of Medicine
The choice of vitamin D formulation matters. Cholecalciferol (vitamin Dâ) remains appropriate for most patients, but in settings where hepatic conversion, intestinal absorption, or tissue bioavailability is impaired, alternative formulations such as calcifediol may offer more predictable increases in circulating 25-hydroxyvitamin D levels.25 In advanced kidney disease, active vitamin D analogs (e.g., calcitriol) may be necessary to manage secondary hyperparathyroidism, but they carry a higher risk of hypercalcemia and require close monitoring.25
Supplementation strategies should prioritize individualized dosing, avoid excessive bolus regimens, and align with clinical goals, such as bone protection, rather than targeting arbitrary serum thresholds.25 For healthcare teams, these findings support a patient-centered, risk-based approach to vitamin D testing, formulation selection, dosing frequency, and counseling.
Vitamin D Toxicity
Vitamin D toxicity, also known as hypervitaminosis D, is an uncommon but potentially serious condition resulting from elevated circulating levels of vitamin D metabolites, usually due to prolonged use of high-dose supplements rather than sun exposure or diet.26 Markedly elevated serum 25-hydroxyvitamin D [25(OH)D] concentrations (typically >150 ng/mL) lead to increased intestinal calcium absorption and bone resorption, resulting in hypercalcemia, which is the primary cause of clinical manifestations.26
Patients with vitamin D toxicity often present with symptoms caused by hypercalcemia, including nausea, vomiting, polyuria, polydipsia, dehydration, confusion, abdominal pain, weakness, and, in severe cases, neuropsychiatric changes or acute kidney injury.26 Less common but serious complications include nephrocalcinosis, soft tissue and vascular calcification, arrhythmias, and renal failure.26 Although rare, cases have occurred due to inadvertent overdosing, manufacturing errors, or underlying metabolic abnormalities that alter vitamin D metabolism, highlighting the importance of monitoring and individualized dosing when using high-dose supplementation.
Applying Vitamin D Evidence in Clinical Practice: Roles of the Healthcare Team
The expanding body of evidence on vitamin D has important implications for routine clinical care. Physicians play a central role in determining when vitamin D testing or supplementation is clinically indicated, particularly in patients with osteoporosis, malabsorptive conditions, chronic kidney disease, or other established risk factors. Pharmacists complement this role by identifying inappropriate or duplicative supplementation, ensuring accurate dosing of over-the-counter products, and counseling patients on formulation selection and adherence. Effective interprofessional collaboration is essential to reduce unnecessary laboratory testing, prevent excessive supplementation, and align vitamin D use with evidence-based indications rather than patient demand or observational associations.
Common Clinical Pitfalls in Vitamin D Testing and Supplementation
Despite an increased awareness of vitamin Dâs role in health, several common pitfalls persist in clinical practice. Routine screening of asymptomatic, low-risk adults remains common despite a lack of supporting evidence and often leads to unnecessary follow-up testing and treatment.5 Another frequent challenge is dose escalation aimed at achieving arbitrary serum 25-hydroxyvitamin D targets in patients without deficiency.5
Healthcare professionals may also underestimate cumulative vitamin D exposure from multiple over-the-counter products, highlighting the importance of thorough medication reconciliation and patient education.
Reassessing and De-escalating Vitamin D Therapy
Vitamin D supplementation is frequently initiated empirically and continued indefinitely without reassessment. In vitamin Dâreplete patients receiving chronic high-dose supplementation, healthcare professionals should periodically assess ongoing need and consider reducing the dose or discontinuing supplementation when appropriate.5 This is important for older adults and those receiving doses well above recommended intakes without a clear clinical indication. Pharmacists play a critical role in identifying opportunities for de-escalation, flagging excessive dosing, and supporting safe deprescribing in collaboration with prescribers.
Counseling Patients and Managing Expectations
Patient expectations surrounding vitamin D may be shaped by media coverage and observational research suggesting broad health benefits. Primary care physicians and pharmacists must be prepared to explain that although vitamin D is essential for bone health and deficiency correction, supplementation has not been shown to prevent most chronic diseases in vitamin Dâreplete individuals. Clear communication regarding the limits of current evidence, the risks of excessive supplementation, and the rationale for avoiding unnecessary testing can support shared decision-making and strengthen patient trust. Framing vitamin D as a targeted therapy rather than a universal preventive intervention is key to aligning care with best available evidence.
Patient Case
Mrs. J. is a 71-year-old woman with a history of osteoporosis and presenting with polymyalgia rheumatica. She rarely spends time outdoors, is lactose intolerant, and takes prednisone 5 mg daily for the rheumatica.
Next Step?
The physician orders labs, including vitamin D and calcium, and assesses fall risk. Recent labs show 25-hydroxyvitamin D at 10 ng/ml, and other labs are normal, including calcium. Laboratory results also show normal kidney and liver function. The physician shares the labs and diagnosis with the pharmacist and explains to the patient that the goal is to correct the vitamin D deficiency.
What is a possible vitamin D treatment plan?
Because of the documented vitamin D deficiency, osteoporosis, and prednisone use, she is an appropriate candidate for treatment rather than routine preventative dosing. The pharmacist completes medication reconciliation, counsels the patient on the goal of correcting vitamin D deficiency, and explains that 5-20 minutes of sun exposure a few days per week can also improve vitamin D levels. The pharmacist asks the patient about over-the-counter medications.
Which vitamin D replacement could be prescribed?
The patient is advised to take Cholecalciferol 2,000-4,000 IU once daily with a meal and to return to the physician in 8-12 weeks.
What is a possible next step?
Based on follow-up appointment, lab results, and reassessment in 8-12 weeks, the dose may be reduced to 1,000 IU daily. Subsequent monitoring of 25-hydroxyvitamin D and calcium occurs after 3-4 months. The patient is educated regarding adequate calcium intake from diet and/or supplements.
Summary
Vitamin D is essential for calcium absorption and skeletal health, and identifying and correcting true deficiency remains an important component of clinical care. However, evidence from large randomized controlled trials has consistently shown that routine vitamin D supplementation in vitamin Dâreplete adults does not meaningfully prevent fractures, cardiovascular disease, cancer, type 2 diabetes, or most other chronic conditions, despite earlier observational associations.
Contemporary guidelines now emphasize a more targeted, evidence-based approach that prioritizes risk-based screening and supplementation for select populations rather than routine testing or empiric high-dose use. For healthcare teams, this shift underscores the importance of avoiding low-value screening, minimizing excessive or duplicative supplementation, counseling patients on realistic expectations, and periodically reassessing ongoing therapy to ensure vitamin D use aligns with demonstrated clinical benefit and patient-specific risk.
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