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Are there prophylactic effects of vitamin D among healthier adult patients? A systematic review of randomized controlled trials.

  • 2025-07-04
  • BMC nutrition 11(1)
    • Caroline Goswami
    • Sherrice Law
    • Hannah Zhang
    • Hannah Park
    • Bhagvat Maheta
    • Katherine Arnott
    • Megan Hsu
    • Kevin Truong
    • Mark Sheffield
    • Zahid Iqbal
    • Chainaronk Limanon
    • David Pai

Study Design

Type
Systematic Review
Sample size
n = 415
Population
healthy adults
Methods
Using PubMed, EMBASE, and Scopus databases, 10,155 articles on vitamin D prophylaxis were identified. Randomized controlled trials targeting healthy patients receiving vitamin D for prophylaxis were included, with exclusions based on language, absence of reported outcomes, and patient history. Articles were screened and evaluated by Covidence and the Cochrane Risk of Bias tool, respectively. Dosage, form, frequency, duration, follow-up care, outcomes, and complications of included articles were recorded.

Introduction

In 2017, a study uncovered increasing trends in vitamin D supplementation, revealing that 18% of adults exceeded 1000 international units (IU) daily, and 3% surpassed the safe limit of 4000 IU, raising concern for severe hypercalcemia and associated pathological effects on the kidneys, heart, and vascular system. While vitamin D is well-established for prophylactic use against osteomalacia and osteoporosis, its extra-skeletal benefits for healthy individuals, such as improving insulin sensitivity and low-density lipoprotein, remain unclear. This study focuses on defining healthy adults and exploring the potential benefits and drawbacks of prophylactic vitamin D supplementation.

Methods

Using PubMed, EMBASE, and Scopus databases, 10,155 articles on vitamin D prophylaxis were identified. Randomized controlled trials targeting healthy patients receiving vitamin D for prophylaxis were included, with exclusions based on language, absence of reported outcomes, and patient history. Articles were screened and evaluated by Covidence and the Cochrane Risk of Bias tool, respectively. Dosage, form, frequency, duration, follow-up care, outcomes, and complications of included articles were recorded. This study protocol has been registered to PROSPERO: CRD42023446944.

Results

Out of 18 articles, 4,415 patients showed low bias risk by the Cochrane tool. Seven studies found significant improvements: protection against autoimmune reactions, elevated hematological and iron profiles, reduced influenza-like illness, and enhanced cognitive tasks. 5000 IU Vitamin D for four weeks significantly reduced cholesterol, unlike 1000 IU for 16 weeks. Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

Conclusion

Except for a few outcomes, most prophylactic Vitamin D supplementation was generally not found to have statistically significant benefits in the healthy adult population. Future directions can include additional prospective studies with larger sample sizes of healthy adults testing for benefits and adverse effects of prophylactic vitamin D use.

Research Insights

  • Vitamin D→Enhanced Cognitive Function

    ...enhanced cognitive tasks.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified
  • Vitamin D→Increased Hemoglobin Levels

    Seven studies found significant improvements: protection against autoimmune reactions, elevated hematological and iron profiles...

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified
  • Vitamin D→Reduced Autoimmune Reaction

    Seven studies found significant improvements: protection against autoimmune reactions...

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified
  • Vitamin D→Reduced Blood Cholesterol

    5000 IU Vitamin D for four weeks significantly reduced cholesterol, unlike 1000 IU for 16 weeks.

    Effect
    Neutral
    Effect size
    Small
    Dose
    1000 IU
  • Vitamin D→Reduced Blood Pressure

    Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified
  • Vitamin D→Reduced Body Mass Index

    Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified
  • Vitamin D→Reduced Hemoglobin A1c

    Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified
  • Vitamin D→Reduced Influenza-Like Illness

    ...reduced influenza-like illness, and enhanced cognitive tasks.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    not specified
  • Vitamin D→Reduced Low-Density Lipoprotein Level

    Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified
  • Vitamin D→Reduced Respiratory Infection

    Conversely, 11 studies revealed no Vitamin D impact on outcomes including hemoglobin-A1c, lipoproteins, BMI, blood pressures, and respiratory infections.

    Effect
    Neutral
    Effect size
    Small
    Dose
    not specified
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