Effect of Calcifediol on Physical Performance and Muscle Strength Parameters: A Systematic Review and Meta-Analysis

There is general agreement that optimal vitamin D status is necessary for bones, muscles, and general health, particularly in older adults, who are at higher risk of negative consequences of vitamin D deficiency, including sarcopenia; vitamin D supplementation is proposed as a potential intervention to mitigate sarcopenia. Several RCTs have reported that calcifediol (25(OH)D) was more potent than cholecalciferol in increasing plasma 25(OH)D. The present systematic review and meta-analysis aimed to summarize the effects of calcifediol on physical performance and muscle strength. We searched databases from inception to 1 January 2022 for studies investigating calcifediol on physical performance or muscle strength parameters. We calculated the difference between the means of follow-up vs. baseline data using standardized mean differences (SMD) and their 95% confidence intervals (CIs); a random-effect model was considered for all of the analyses. Seven RCTs were included in the meta-analysis. Calcifediol significantly improved gait speed (SMD = 2.500; 95%CI = 1.768-3.223; p < 0.0001); handgrip strength (n = 5446 participants, SMD = 0.532; 95%CI: 0.305-0.758; p < 0.0001; I-2 = 20.2%); and leg extension (n = 4318 participants, SMD = 0.641; 95%CI: 0.346 to 0.935; p < 0.0001; I-2 = 18.8%;) vs. baseline values. In conclusion, in this systematic review and meta-analysis, we observed that calcifediol may have a positive effect on muscle strength parameters, with less evidence on physical performance. These data further indicate the importance of vitamin D and, in particular, of calcifediol, not only on bone metabolism but also on muscle parameters and sarcopenia.