Background: Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them. Methods: We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease. Results: A total of 13 double-blind, placebo-controlled RCTs (14,692 participants in an intervention group and 14,243 participants in a control group) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06–1.25, I2 = 0.0%, n = 14) and CHD (RR 1.16, 95% CI 1.05–1.28, I2 = 0.0%, n = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700–1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD. Conclusions: The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.
We investigated whether cellular phone use was associated with increased risk of tumors using a meta-analysis of case-control studies. PubMed and EMBASE were searched from inception to July 2018. The primary outcome was the risk of tumors by cellular phone use, which was measured by pooling each odds ratio (OR) and its 95% confidence interval (CI). In a meta-analysis of 46 case-control studies, compared with never or rarely having used a cellular phone, regular use was not associated with tumor risk in the random-effects meta-analysis. However, in the subgroup meta-analysis by research group, there was a statistically significant positive association (harmful effect) in the Hardell et al. studies (OR, 1.15—95% CI, 1.00 to 1.33— n = 10), a statistically significant negative association (beneficial effect) in the INTERPHONE-related studies (case-control studies from 13 countries coordinated by the International Agency for Research on Cancer (IARC); (OR, 0.81—95% CI, 0.75 to 0.89—n = 9), and no statistically significant association in other research groups’ studies. Further, cellular phone use with cumulative call time more than 1000 h statistically significantly increased the risk of tumors. This comprehensive meta-analysis of case-control studies found evidence that linked cellular phone use to increased tumor risk.
Humans are exposed to a mixture of metals during their lifetime; however, evidence of neurotoxicity of such mixtures in critical time windows is still insufficient. We aimed to elucidate the associations of four metals mixture across multiple time points with children's intelligence quotient (IQ) in a prospective cohort study. Prenatal exposure and exposure at age 4 and 6 years to four types of blood metals, namely lead, mercury, cadmium, and manganese were quantified in 502 pregnant women and their children who participated in the Environment and Development Cohort study. Children' s IQ scores were assessed using the Wechsler Intelligence Scale at age 6. Bayesian kernel machine regression (BKMR), quantile g-computation models, and elastic net (ENET) models were used to assess the associations of their blood metals mixture with IQ scores. Multivariate linear regression models indicated that postnatal blood manganese exposure at the age of 4 years was significantly negatively associated with children's IQ [β = - 5.99, 95% confidence interval (CI): -11.37 to - 0.61]. In the multi-chemical BKMR and quantile g-computation model, statistically significant inverse associations were found between the mixture of prenatal and postnatal metals and children's IQ score (Difference in children' IQ per quartile increase: -2.83; 95% CI: -5.28, -0.38). Interestingly, we found that manganese levels at both age of 4 and 6 years were contributing factors to children's IQ in the mixture models, namely, BKMR, quantile g-computation, and ENET models. Multi-pollutant mixtures of prenatal and postnatal exposures to four metals affected child IQ at 6 years of age. We found a relationship between manganese exposure at both age 4, and 6 years and children's IQ. Additional studies are warranted to confirm these associations and to control the exposure to different metals during pregnancy and preschool childhood.