International journal of bipolar disorders · 2026
Vitamin D and calcium metabolism in bipolar disorder: a scoping review of contradictory evidence.
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Kulmagambetov Amirzhan, Tmava-Berisha Adelina, Fellendorf Frederike T, Lenger Melanie, Stross Tatjana, Stijic Marko, Fleischmann Eva, Ilić Julia, Finner Alexander, Ramirez-Obermayer Anna, Georgi Johanna, Maget Alexander, Lässer Amrei, Mittmannsgruber Claudia, Smolle Stefan, Häussl Alfred, Schuller Jonas, Hasic Dino, Bengesser Susanne, Queissner Robert, Dalkner Nina, Reininghaus Eva Z
Аннотация
BACKGROUND: This scoping review synthesized evidence on vitamin D, parathyroid hormone (PTH), and serum calcium in bipolar disorder (BD) to evaluate their potential clinical utility.
METHODS: A systematic PubMed search identified original studies examining calcium metabolism biomarkers (vitamin D, PTH, serum calcium) exclusively in BD populations. Findings were synthesized narratively due to substantial methodological heterogeneity.
RESULTS: Fourteen studies met inclusion criteria, with small sample sizes (median n = 55) and predominantly cross-sectional designs. Vitamin D comparisons between BD patients and controls yielded contradictory results: three studies reported significantly lower levels in BD patients, two found significantly higher levels, and three found no differences. Vitamin D deficiency definitions varied widely (< 25 to < 50 nmol/L), precluding meaningful comparisons. Four cognition studies showed inconsistent associations with vitamin D, with negative correlations, age-dependent effects, or no associations reported. Two small vitamin D supplementation studies in bipolar spectrum disorders yielded contradictory results in distinct populations, with one in youth and the other in adults. Data on PTH and calcium were sparse and inconsistent.
LIMITATIONS: Study limitations included a single database search, substantial study heterogeneity, and inadequate control for confounders, including seasonal variation.
CONCLUSIONS: Evidence on calcium metabolism biomarkers in BD is contradictory and methodologically limited. Fundamental inconsistencies in vitamin D status between BD patients and controls, combined with conflicting supplementation data, preclude clinical recommendations. Routine vitamin D screening specifically for BD management cannot be supported. Large-scale, standardized studies are needed before clinical application.
METHODS: A systematic PubMed search identified original studies examining calcium metabolism biomarkers (vitamin D, PTH, serum calcium) exclusively in BD populations. Findings were synthesized narratively due to substantial methodological heterogeneity.
RESULTS: Fourteen studies met inclusion criteria, with small sample sizes (median n = 55) and predominantly cross-sectional designs. Vitamin D comparisons between BD patients and controls yielded contradictory results: three studies reported significantly lower levels in BD patients, two found significantly higher levels, and three found no differences. Vitamin D deficiency definitions varied widely (< 25 to < 50 nmol/L), precluding meaningful comparisons. Four cognition studies showed inconsistent associations with vitamin D, with negative correlations, age-dependent effects, or no associations reported. Two small vitamin D supplementation studies in bipolar spectrum disorders yielded contradictory results in distinct populations, with one in youth and the other in adults. Data on PTH and calcium were sparse and inconsistent.
LIMITATIONS: Study limitations included a single database search, substantial study heterogeneity, and inadequate control for confounders, including seasonal variation.
CONCLUSIONS: Evidence on calcium metabolism biomarkers in BD is contradictory and methodologically limited. Fundamental inconsistencies in vitamin D status between BD patients and controls, combined with conflicting supplementation data, preclude clinical recommendations. Routine vitamin D screening specifically for BD management cannot be supported. Large-scale, standardized studies are needed before clinical application.