It has long been known that insulin-like growth factor 1 (IGF1) causes an increase in the circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), the hormonally active vitamin D metabolite, by stimulating the expression and activity of the 1α-hydoxylase that produces 1,25(OH)2D in the kidney. Indeed, plasma 1,25(OH)2D is significantly higher in active than controlled acromegaly, with a tendency to hypercalcemia, hyperphosphatemia, and hypercalciuria. On the other hand, more recent data has suggested that vitamin D may contribute to determining IGF1 concentrations. Mice knockout for the vitamin D receptor (VDR) exhibit 30% lower IGF1 levels compared with WT animals and a significant increase in serum IGF1 was noted in response to vitamin D in two small cohorts of children. Furthermore, cross-sectional analyses of community-based cohorts disclosed a positive correlation between the concentrations of 25-hydroxyvitamin D (25(OH)D), the marker of vitamin D status, and IGF1. Here we first conducted an open-label, controlled study of the changes in circulating IGF1 following vitamin D supplementation in adults. Then, we asked whether the influence of vitamin D on IGF1 might be clinically relevant for the management of growth hormone deficiency (GHD), which relies on measurement of IGF1 levels.


Previous studies suggested that vitamin D modulates circulating IGF1. We investigated this effect in adults and its clinical relevance in the management of GH deficiency (GHD).
IGF1 levels were prospectively measured before and after 12 weeks of treatment with oral vitamin D3 (5000 or 7000 IU/week) vs no intervention in 39 subjects 61.9±7.9 years old. The frequency of IGF1 values ≥50th age- and sex-specific percentile in relation to vitamin D status, as determined by the concentration of 25-hydroxyvitamin D (25(OH)D), was retrospectively assessed in 69 GHD patients (57.4±16.6 years) on stable hormone replacement and with 25(OH)D and IGF1 concurrently measured.
Treatment with 5000 and 7000 IU vitamin D3/week significantly raised 25(OH)D by 12.7±8.4 and 13.1±6.5 ng/ml respectively (both P<0.001 vs baseline). In the 7000 IU group, IGF1 levels also significantly increased by 31.3±36.7 ng/ml (P=0.01). Neither 25(OH)D nor IGF1 significantly varied in controls. IGF1 was ≥50th percentile more frequently in GHD patients with 25(OH)D levels ≥15 than <15 ng/ml (65.9 vs 40.0%, P<0.05). Logistic regression with adjustment for recombinant human GH (rhGH) dose, vitamin D supplements, gender, use of thyroid hormones, corticosteroids or estrogen/testosterone, and season revealed a significant positive association between ≥15 ng/ml 25(OH)D and IGF1 ≥50th percentile (OR 4.4, 95% CI 1.0-18.8, P<0.05). A significant negative correlation between 25(OH)D concentrations and rhGH dose was found after correcting for age and IGF1 (β -0.042, P<0.01), but not after further adjusting for sex, thyroid, adrenal or gonadal replacement, and season (β -0.037, P=0.06).
Vitamin D increases circulating IGF1 in adults. As a result, a better vitamin D status may ease the achievement of normal IGF1 values in GHD."