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Association between blood lead levels and markers of calcium homeostasis: a systematic review and meta-analysis.
Upadhyay, K, Viramgami, A, Bagepally, BS, Balachandar, R
Scientific reports. 2022;(1):1850
Abstract
Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I2 statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I2 > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure.
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Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.
Wu, Y, Huang, R, Wang, M, Bernstein, L, Bethea, TN, Chen, C, Chen, Y, Eliassen, AH, Freedman, ND, Gaudet, MM, et al
The American journal of clinical nutrition. 2021;(2):450-461
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BACKGROUND Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials.
Myung, SK, Kim, HB, Lee, YJ, Choi, YJ, Oh, SW
Nutrients. 2021;(2)
Abstract
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 (n = 28,935 participants in an intervention group and 14,243 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.
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Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis.
Zhang, Y, Li, Y, Liu, J, Wei, X, Tan, N, Zhang, J, Wang, W, Wang, Y
The journal of nutrition, health & aging. 2021;(2):263-270
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BACKGROUND To exploring the role of vitamin D or calcium supplementation in reducing all-cause mortality and cardiovascular outcomes. METHODS The search was restricted to systematic reviews or meta-analyses published from January 1, 2010, to July 7, 2019. An additional search was performed to identify recently published randomized controlled trials (from January 1, 2015, to July 7, 2019). Homogeneous results from different studies were pooled using Revman 5.3 software. RESULTS Twenty-three studies involving 89,251 participants were ultimately included in this meta-analysis. No associations were observed between the supplementation and composite cardiovascular outcomes, consisting of all-cause mortality, cardiovascular mortality, myocardial infarction, and other MACEs. CONCLUSIONS Whether used alone or in combination, vitamin D and calcium supplementation do not exert meaningful effects on all-cause mortality, cardiovascular mortality, MACEs or MI among community-dwelling adults.
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Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis.
Pana, TA, Dehghani, M, Baradaran, HR, Neal, SR, Wood, AD, Kwok, CS, Loke, YK, Luben, RN, Mamas, MA, Khaw, KT, et al
European journal of epidemiology. 2021;(7):669-683
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The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40-79 years were followed up for a median of 20.36 years (20.32-20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women.
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Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects.
Lo-Kioeng-Shioe, MS, Rijlaarsdam-Hermsen, D, van Domburg, RT, Hadamitzky, M, Lima, JAC, Hoeks, SE, Deckers, JW
International journal of cardiology. 2020;:56-62
Abstract
BACKGROUND Coronary artery calcium (CAC) scanning has evolved into an important subclinical prediction method for cardiovascular diseases in asymptomatic subjects. However, the prognostic implication of CAC scanning in symptomatic individuals is less clear. OBJECTIVES To assess the prognostic utility of CAC in predicting risk of major adverse cardiac events (MACE) in stable patients with suspected CAD. METHODS We did a systematic electronic literature search for studies presenting original data in CAC score, and reporting cardiovascular events in stable, symptomatic patients as primary outcome. Primary outcome of the meta-analysis was the occurrence of MACE, a composite of late coronary revascularization, hospitalization for unstable angina or heart failure, nonfatal myocardial infarction, and cardiac death or all-cause mortality. Using random effects models, we pooled relative risk ratios of CAC for MACE, and adjusted hazard ratios (HR) of the associations between different CAC strata (CAC 0-100,100-400, and ≥ 400, versus CAC = 0) and incident MACE. RESULTS We included 19 observational studies (n = 34,041). In total, 1601 events were analyzed, of which 158 in patients with CAC = 0. The pooled relative risk ratio was 5.71 (95%-CI: 3.98;8.19) for subjects with CAC > 0. The pooled estimate of adjusted HRs demonstrated increasing, positive associations, with the strongest association for CAC > 400 (HR: 4.88; 95%-CI: 2.44;9.27). CONCLUSIONS This meta-analysis demonstrated that increased levels of CAC are strongly and independently associated with increased risk for MACE in stable, symptomatic patients with suspected CAD, showing increasing risk with greater CAC scores. Application of CAC scanning as a prediction method could be useful for a considerable number of such patients.
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The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function: A Systematic Review and Meta-Analysis.
Xia, C, Vonder, M, Sidorenkov, G, Oudkerk, M, de Groot, JC, van der Harst, P, de Bock, GH, De Deyn, PP, Vliegenthart, R
Journal of atherosclerosis and thrombosis. 2020;(9):934-958
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AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p<0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.
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Calcium supplementation for improving bone density in lactating women: a systematic review and meta-analysis of randomized controlled trials.
Cai, G, Tian, J, Winzenberg, T, Wu, F
The American journal of clinical nutrition. 2020;(1):48-56
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BACKGROUND Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. OBJECTIVES We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. METHODS An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. CONCLUSIONS Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.
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Effect of Calcium and Vitamin D Co-supplementation on Blood Pressure: A Systematic Review and Meta-Analysis.
Morvaridzadeh, M, Sepidarkish, M, Fazelian, S, Rahimlou, M, Omidi, A, Ardehali, SH, Sanoobar, M, Heshmati, J
Clinical therapeutics. 2020;(3):e45-e63
Abstract
PURPOSE Vitamin D and calcium insufficiency has been related to elevated blood pressure (BP) and cardiovascular complications. This systematic review and meta-analysis investigates the effect of calcium and vitamin D co-supplementation on BP. METHODS A systematic search was conducted of electronic databases, including Web of Sciences, MEDLINE, Scopus, EMBASE, and the Cochrane Library, along with searches of gray literature and reference lists from included trials. There were no language restrictions, and the databases were searched from inception to October 2019. Randomized controlled trials, using calcium and vitamin D co-supplementation and reporting mean systolic BP and/or diastolic BP (DBP) with SDs, were included in the systematic review. Articles were evaluated independently by 2 researchers based on inclusion and exclusion criteria. A random effects model was conducted to synthesize the data. FINDINGS Eight trials were included in the meta-analysis. Meta-analysis of these 8 trials indicated a nonsignificant reduction in systolic BP in the calcium and vitamin D co-supplementation group compared with control (standardized mean difference, -0.23; 95% CI, -0.52 to 0.06). Conversely, there was a statistically significant decrease in DBP (standardized mean difference, -0.29; 95% CI, -0.55 to -0.02). Subgroup analysis suggested that young adults achieve a greater reduction in DBP than other age groups. IMPLICATIONS Calcium and vitamin D co-supplementation can modulate DBP and should be investigated more specifically in large, well-designed trials of hypertensive populations. (Clin Ther. 2020;42:XXX-XXX) © 2020 Elsevier HS Journals, Inc.
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Comparison of fracture risk using different supplemental doses of vitamin D, calcium or their combination: a network meta-analysis of randomised controlled trials.
Hu, ZC, Tang, Q, Sang, CM, Tang, L, Li, X, Zheng, G, Feng, ZH, Xuan, JW, Shen, ZH, Shen, LY, et al
BMJ open. 2019;(10):e024595
Abstract
OBJECTIVE Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN A systematic review and network meta-analysis. DATA SOURCES Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER CRD42017079624.