Abstract
Simple SummarySkeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. It is unknown if high-dose vitamin D3 impacts skeletal muscle and adipose tissue, as compared with standard-dose vitamin D3, in patients with advanced or metastatic colorectal cancer. In this exploratory analysis of a phase II randomized trial, high-dose vitamin D3 did not lead to changes of body weight, body mass index, muscle area, muscle attenuation, visceral adipose tissue area, or subcutaneous adipose tissue area, as compared with standard-dose vitamin D3. High-dose vitamin D3 did not change body composition in patients receiving chemotherapy for advanced or metastatic colorectal cancer.Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D3 (4000 IU) or standard-dose (400 IU) vitamin D3. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D3, high-dose vitamin D3 did not significantly change body weight [−0.7 kg; (95% CI: −3.5, 2.0)], body mass index [−0.2 kg/m2; (95% CI: −1.2, 0.7)], muscle area [−1.7 cm2; (95% CI: −9.6, 6.3)], muscle attenuation [−0.4 HU; (95% CI: −4.2, 3.2)], visceral adipose tissue area [−7.5 cm2; (95% CI: −24.5, 9.6)], or subcutaneous adipose tissue area [−8.3 cm2; (95% CI: −35.5, 18.9)] over the first 8 cycles of chemotherapy. Among patients with advanced or metastatic colorectal cancer, the addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy did not result in any changes in body composition.
Highlights
More than 80% of the U.S population has vitamin D insufficiency (e.g., 25-hydroxyvitamin D [25(OH)D] concentrations ≤30 ng/mL) [1]
139 participants were randomized; 105 participants were evaluable in this exploratory analysis, did not differ between groups (p = 0.32); the most common reason participants were not included in which did not differ between groups (p = 0.32); the most common reason participants were not this analysis was because the obtained computed tomography image needed to quantify body included in this analysis was because the obtained computed tomography image needed to quantify composition was of insufficient quality or did not include the abdominal region (Figure 1)
Baseline muscle area and visceral adipose tissue area were associated with overall survival and change in muscle attenuation from baseline to cycle 8 was associated with progression-free survival
Summary
More than 80% of the U.S population has vitamin D insufficiency (e.g., 25-hydroxyvitamin D [25(OH)D] concentrations ≤30 ng/mL) [1]. Observational studies report that vitamin D insufficiency is independently associated with a higher risk of cancer death [2,3]. Meta-analyses of randomized controlled trials demonstrate that vitamin D supplementation reduces cancer death [4,5]. The mechanisms through which vitamin D supplementation may slow cancer progression and reduce cancer death are incompletely understood [6,7]. In skeletal muscle, binding of the vitamin D receptor stimulates protein synthesis, resulting in muscle cell proliferation and growth [12,13]. Detailed reviews of these biological relationships have been reviewed elsewhere [14,15]
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