**Background:** Multiple myeloma (MM) is a hematologic malignancy with rising global incidence, increasing by 126% between 1990 and 2016. Despite advances in therapy, MM remains incurable. Pre-clinical evidence suggests vitamin D may influence MM through differentiation of malignant cells, immune modulation, and synergy with conventional treatment. This scoping review aimed to map human-level research on the association between vitamin D and MM risk, prognosis, and symptom burden.
**Methods:** A structured scoping review was conducted following PRISMA-ScR guidelines. Three databases (OVID-Medline, OVID-Embase, OVID-Cochrane Library) were searched on August 18, 2021, without time restrictions. Two independent reviewers screened titles/abstracts and full texts. Inclusion criteria required primary research on vitamin D (all natural forms) or VDR in populations with MM, MGUS, or smoldering myeloma, reporting clinical outcomes. Exclusion criteria included grey literature, non-primary research, synthetic vitamin D analogues, and pre-clinical studies. Data extraction covered study characteristics, vitamin D status definitions, serum 25(OH)D levels, clinical outcomes, and safety.
**Key Results:** The search yielded 1,471 records; after deduplication and screening, 15 publications (14 studies) were included. All were observational: four cross-sectional (yielding five publications), three retrospective cohorts, two case-control studies, one cross-sectional with retrospective chart review, one retrospective chart review, one matched controlled cohort, one prospective cohort, and one case report. No experimental studies were identified. The most common vitamin D deficiency cutoff was <50 nmol/L (<20 ng/mL) 25(OH)D (n=9 publications), and sufficiency cutoff was >75 nmol/L (>30 ng/mL) (n=6). Among ten publications reporting deficiency prevalence, the median percentage of vitamin D deficient patients was 42.3% (range: 23.7% to 100%). Sex differences were noted: median deficiency in females was 44.95% (range: 34.3%–54.6%) and in males 55.1% (range: 45.4%–65.7%). No studies reported on vitamin D status and risk of developing MM. For prognosis, two of three studies found an association between deficiency and poorer survival. Three of five studies reported higher MM stage with lower vitamin D levels. Evidence on peripheral neuropathy was conflicting: one study found an association with severity, two found deficiency increased occurrence, and one found no association. Most studies (four of five) found no significant association between vitamin D and bony disease. Three VDR polymorphism studies reported that the FokI f, ApaI a, and BsmI b alleles were significantly associated with increased MM risk (e.g., FokI ff vs. FF genotype OR: 5.33, p<0.0001 in one study).
**Clinical Implications:** Vitamin D deficiency is prevalent in MM patients, and lower levels may be associated with higher disease stage and worse survival, though evidence is limited by observational designs and heterogeneity in vitamin D status definitions. The absence of studies on vitamin D and MM risk represents a critical knowledge gap. VDR polymorphisms may identify genetic targets for risk stratification. The authors call for experimental studies to determine whether vitamin D optimization—a low-cost intervention—could impact MM progression, symptom burden (particularly peripheral neuropathy), and survival. Standardized vitamin D status definitions are needed for future research.