Vitamin D-fortified foods are a proven effective method of improving vitamin D status (1) ; however, the magnitude of the effect varies across populations and interventions (2) . This conservative meta-analysis and meta-regression aimed to assess the overall effect of vitamin D-fortified foods on serum 25-hydroxyvitamin D (25(OH)D) concentrations and to explore potential moderators influencing this response. A literature search of PubMed was conducted on 23 January 2024. A conservative approach was taken, with RCTs only eligible for inclusion if the control and intervention foods were identical, apart from vitamin D fortification of the treatment arm, allowing the effect of fortification to be isolated with minimal risk of confounding. Of 701 publications identified by the initial search, 25 studies were deemed eligible for inclusion. A random-effects meta-analysis was conducted to estimate the overall effect of fortification on serum 25(OH)D concentrations. Due to the limited number of studies, univariate meta-regression analyses were used to test potential moderators. Baseline serum 25(OH)D, vitamin D dose, intervention duration, sample size, and food type (animal or plant based) were included in this analysis. Significant moderators were then incorporated into a final multivariate model. Sensitivity analyses were performed to evaluate the robustness of findings. Random effects meta-analysis found that vitamin D-fortified foods significantly increase serum 25(OH)D concentrations (weighted mean difference: 24.4 nmol/L, 95% CI: 17.4 to 31.5, p < 0.001) but substantial heterogeneity (I 2 = 98%) was present. Meta-regression revealed that baseline serum 25(OH)D (p = 0.002) and dose (p < 0.001) were significant independent predictors of response, explaining 53.9% of the between-study variance (R 2 = 53.9%). Leave-one-out analysis identified two studies of note: exclusion of an outlier study, with an exceptionally high dose, reduced model fit and rendered dose non-significant (R 2 = 36.5%, dose p = 0.058), whereas removal of a second influential study increased model fit (R 2 = 72.5%). A model excluding both studies explained 61.8% of the heterogeneity, with dose (p = 0.004) and baseline 25(OH)D (p < 0.001) remaining significant predictors. This confirms the effectiveness of vitamin D-fortified foods in raising serum 25(OH)D concentrations, however, the degree of response is influenced by baseline 25(OH)D and dose, with poorer baseline status and higher doses generally producing greater increases. Surprisingly, duration was not found to moderate response, perhaps due to lower compliance at longer durations, or a reduced effect as concentrations increased. Substantial heterogeneity remains, suggesting the contribution of additional unmeasured factors.
Robertson et al. (Fri,) studied this question.
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