Determinants of parathyroid hormone response to vitamin D supplementation: a systematic review and meta-analysis of randomised controlled trials.

This systematic review aimed to assess the determinants of the parathyroid hormone (PTH) level response to vitamin D supplementation. We searched Medline, Google Scholar and the reference lists of previous reviews. All randomised controlled trials (RCT) on vitamin D supplementation that involved apparently healthy human subjects with a report of PTH were selected. Potential studies were screened independently and in duplicate. Results are summarised as mean differences with 95% confidence intervals. Quality assessment, subgroup analysis, meta-analysis and meta-regression analysis were carried out. Thirty-three vitamin D supplementation RCT were included. Vitamin D supplementation significantly raised circulating 25-hydroxyvitamin D (25(OH)D) with significant heterogeneity among studies with a pooled mean difference (PMD) of 15.5 ng/ml (test for heterogeneity: P<0·001 and I 2=97·3%). Vitamin D supplementation significantly reduced PTH level with PMD of -8·0 pg/ml, with significant heterogeneity ((test for heterogeneity: P<0·001) and the I 2 value was 97·3%). In the subgroup analyses, the optimum treatment effect for PTH was observed with Ca doses of 600-1200 mg/d (-22·48 pg/ml), after the duration of a >12-month trial (-18·36 pg/ml), with low baseline 25(OH)D concentration of <20 ng/ml (-16·70 pg/ml) and in those who were overweight and obese (-18·11 pg/ml). Despite the present meta-analysis being hindered by some limitations, it provided some interesting evidence, suggesting that suppression of PTH level needs higher vitamin D intake (75 μg/d) than the current recommendations and longer durations (12 months), which should be taken into account for nutritional recommendations.