Effects of calcium and calcium plus vitamin D supplementation on cardio-cerebrovascular outcomes and risk factors: an evidence map, umbrella review, and updated meta-analysis

Abstract

Content of image described in text. Abstract This umbrella review synthesised evidence from 35 meta-analyses encompassing 154 randomised controlled trials (11 newly included) and 78,175 participants to evaluate the clinical effects of calcium (Ca) and calcium plus vitamin D (CaD) supplementation on cardio-cerebrovascular outcomes and metabolic parameters. Data extracted from Embase, Web of Science, PubMed, and Cochrane Library (inception to 31 January 2025) revealed divergent outcomes: Ca supplementation demonstrated reductions in diastolic blood pressure, body fat, total cholesterol, and total/high-density lipoprotein (HDL) cholesterol ratio but was associated with increased cardio-cerebrovascular disease risk, elevated inflammatory markers (IL-6, TNF-α), two-hour postload glycemia, and waist-to-hip ratio. Conversely, CaD supplementation showed beneficial regulation of cardiovascular risk factors including decreased body fat, body mass index, fasting blood glucose, and improved lipid profiles (low-density lipoprotein, HDL, non-HDL, and total/HDL cholesterol ratios), whereas no significant effects were observed on cardio-cerebrovascular disease incidence. Limitations included exclusion of studies with an unspecified calcium source and suboptimal evidence quality. Taken together, these findings suggest that CaD supplementation may confer a more favourable cardiometabolic profile than Ca supplementation alone. Because several clinical event outcomes were supported by low-certainty evidence, the potential benefits and risks of calcium supplementation should be weighed carefully in individualised clinical decision-making.