Review of Vitamin D Evidence and Controversies - 2026

Vitamin D and Health Outcomes: State-of-the-Art Review of Triangulated Evidence and Ongoing Controversies

Current Nutrition Reports (2026) 15:26 https://doi.org/10.1007/s13668-026-00748-2REVIEW

Maria Dalamaga © • Rodopi Emfietzoglou1 • Dimitra Petropoulou1 • Maria Kypraiou • Dimitris C. Kounatidis • Natalia G. Vallianou • Spyridon Karras • Faidon Magkos • Irene Karampela7

Purpose of Review Vitamin D is a pleiotropic hormone with an established role in skeletal integrity and broader actions in immune regulation, inflammation, cellular proliferation, and energy homeostasis. Despite decades of research, its extra-skel­etal effects remain controversial, largely due to discordant findings across observational studies, Mendelian randomization studies (MRS), and randomized controlled trials (RCTs). Unlike many prior reviews, this state-of-the-art review synthesizes triangulated evidence across these study designs to clarify outcome-specific causal relationships and ongoing controversies.

Recent Findings Triangulated evidence provides strong and consistent support for a causal role of vitamin D in skeletal health, particularly in the prevention and treatment of rickets and osteomalacia, and in fracture risk reduction among vita­min D-deficient and older populations. For selected extra-skeletal outcomes, modest and threshold-dependent benefits are observed, including reductions in cancer mortality, protection against autoimmune disorders, most convincingly multiple sclerosis, and decreased risk of acute respiratory infections, including COVID-19, primarily in individuals with low baseline 25(OH)D concentrations.

In contrast, associations with cardiovascular disease, metabolic disorders, obesity, and most neuro­psychiatric outcomes are not consistently supported by genetic or interventional evidence, suggesting limited or non-causal effects. Across outcomes, evidence indicates a non-linear relationship between vitamin D status and health, with increased risk concentrated at low 25-hydroxyvitamin D concentrations and limited benefit beyond sufficiency.

All-cause mortality shows a modest, threshold-dependent association, with supplementation benefits largely confined to deficient or older popu­lations.

Key challenges include

• assay variability,
• non-linear dose-response relationships, and
• RCT designs that frequently enroll vitamin D-replete populations,
  resulting in substantial methodological heterogeneity and limiting causal inference.

Summary Overall, the presented triangulated model may reconcile longstanding inconsistencies by reframing vitamin D as a context-dependent determinant of health. These findings argue against indiscriminate population-wide supplementation and support targeted strategies focused on the identification and correction of deficiency. Vitamin D should be regarded neither as a universal panacea nor as a trivial supplement, but as a context-dependent hormone whose clinical value lies in outcome-specific correction of deficiency.

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Challenges ignored by the review include:

• Failure to use gut-friendly Vitamin D for people with poor gut function
• Failure to increase the dose size for Overweight/obese people
• Failure to offer other forms when the participant is reluctant to take capsules - 20%?
• RCTs often have poor compliance for daily supplementation.
  Weekly and bi-weekly have much better compliance
• Vitamin D often needs co-factors like Magnesium
• RCTs often choose from a pool of otherwise healthy people. Which is not the real world
• Why Mendelian randomization fails with Vitamin D