{"publication_id":"798fcdb7-5e51-43e8-978e-937dfca0ad1c","content_hash":"sha256:95dffe28700375ce82616ec3189702998282ceb693e1904127f34a9737d2a7ee","nodes":[{"id":"798fcdb7-5e51-43e8-978e-937dfca0ad1c","type":"publication","title":"Adjacent Evidence Brief: Calcium Supplementation Effects — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 24/36 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This synthesis tests the thesis that evidence for Calcium Supplementation Effects is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Calcium supplementation has long been proposed as a low-cost public-health lever for bone, cardiovascular, and pregnancy-related outcomes, yet contemporary evidence has been complicated by discrepant findings across indications, populations, and dosing regimens. We conducted an AI-assisted structured evidence synthesis across the curated source set, applying a transparent audit trail in which each study was tagged for design, directness, outcome class, and direction of effect before integration."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: 24/36 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"This synthesis tests the thesis that evidence for Calcium Supplementation Effects is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation."},{"id":"claim_4","type":"claim","text":"Calcium supplementation has long been proposed as a low-cost public-health lever for bone, cardiovascular, and pregnancy-related outcomes, yet contemporary evidence has been complicated by discrepant findings across indications, populations, and dosing regimens."},{"id":"claim_5","type":"claim","text":"We conducted an AI-assisted structured evidence synthesis across the curated source set, applying a transparent audit trail in which each study was tagged for design, directness, outcome class, and direction of effect before integration."},{"id":"claim_6","type":"claim","text":"Across the corpus, the evidence base is context-dependent rather than uniformly favorable: pre-eclampsia prevention, certain insulin-related endpoints, and selected bone-fracture outcomes show benefit, while older-adult and pregnancy inflammation biomarkers, recurrent cardiovascular events, and several body-composition endpoints remain null or unfavorable, with mechanistic plausibility (Ioannidis 2005) coexisting alongside sparse or mixed human-RCT confirmation."},{"id":"claim_7","type":"claim","text":"We conclude that calcium supplementation should not be framed as a monolithic intervention: the most defensible indications remain high-risk pregnancy, while bone-fracture benefit in community-dwelling older adults and cardiovascular safety in at-risk populations remain insufficiently resolved and warrant further direct, outcome-stratified randomized evaluation."},{"id":"claim_8","type":"claim","text":"Evidence-abstraction note.** The 36 retained reference papers are not 36 independent primary clinical trials: 24 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 12 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_9","type":"claim","text":"This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-calcium_supplementation_effects-v06-DAILY-2026-07-01T12-45-35Z-R2`."},{"id":"claim_10","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_11","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_12","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, immune and inflammation, longevity, muscle function, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_13","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_14","type":"claim","text":"Additional corpus sources included animal/preclinical evidence; | Source | Outcome class | Direction | Directness | Tier | Finding |"},{"id":"claim_15","type":"claim","text":"| Chen 2022 | Cardiometabolic | null | review | B2 | 27 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_16","type":"claim","text":"| Cormick 2020 | Cardiometabolic | unclear | indirect | B2 | representative non-significant statistic P = .408; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_17","type":"claim","text":"| Cormick 2023 | Cardiometabolic | null | review | B2 | 20 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_18","type":"claim","text":"| Cormick 2024 | Cardiometabolic | null | review | B1 | representative non-significant statistic P = 0.45; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_19","type":"claim","text":"| Dwarkanath 2024 | Cardiometabolic | null | direct | A1 | 24 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_20","type":"claim","text":"| Fu 2022 | Cardiometabolic | null | review | B2 | representative non-significant statistic P = 0.65; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_21","type":"claim","text":"| Imdad 2011 | Cardiometabolic | null | review | B2 | 50 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_22","type":"claim","text":"| Korhonen 2022 | Cardiometabolic | unclear | review | B1 | representative non-significant statistic P > 0.05; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_23","type":"claim","text":"| Souza 2014 | Cardiometabolic | null | direct | A1 | representative non-significant statistic P=0.112; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_24","type":"claim","text":"| Zhang 2026 | Cardiometabolic | null | indirect | B2 | 52 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_25","type":"claim","text":"| Zhang 2020 | Longevity | unclear | review | B2 | representative non-significant statistic P = 0.45; not treated as positive or negative directional support unless source direction is coded |"},{"id":"claim_26","type":"claim","text":"| Gupta 2010 | Muscle Function | null | direct | A1 | 4 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_27","type":"claim","text":"| Coombs 2023 | Skeletal, Fracture, and Bone | null | direct | A1 | 18 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"claim_28","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_29","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_30","type":"claim","text":"Direction reconciliation: receipt-level null or unclear coding is conservative claim-level coding. Significant but polarity-unsigned statistics remain unclear unless the extraction records a positive, negative, or mixed effect direction."},{"id":"source_1","type":"source","study":"Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial","year":2022,"doi":"10.1136/bmjopen-2021-060189","url":"https://doi.org/10.1136/bmjopen-2021-060189","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Mundell 2022","excerpt":"OBJECTIVES: The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT). DESIGN: 12-month, two-arm, randomised controlled trial. SETTING: University clinical exercise centre. PARTICIPANTS: 70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36). INTERVENTION: Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%)."},{"id":"source_2","type":"source","study":"Calcium supplementation during pregnancy and long‐term offspring outcome: a systematic literature review and meta‐analysis","year":2022,"doi":"10.1111/nyas.14729","url":"https://doi.org/10.1111/nyas.14729","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Korhonen 2022","excerpt":"The World Health Organization currently recommends calcium supplementation for pregnant women, especially those with low calcium intakes, to reduce the risk of hypertension and preeclampsia. We aimed to evaluate the effect of this intervention on selected offspring outcomes. A systematic search was conducted in 11 databases for published randomized controlled trials (RCTs) on the effect of maternal calcium supplementation with or without vitamin D during pregnancy on selected offspring cardiovascular, growth, and metabolic and neurodevelopmental outcomes. Screening of titles and abstracts of 3555 records and full texts of 31 records yielded six RCTs (nine reports, n = 1616). Forest plot analyses were performed if at least two studies presented comparable data on the same outcome. In one study (n = 591), high-dose calcium supplementation during pregnancy was associated with a decreased risk of offspring high systolic blood pressure at 5-7 years of age (risk ratio = 0.59; 95% confidence interval: 0.39-0.90). The effects of the intervention on offspring growth, metabolic, and neurodevelopmental outcomes remain unknown because of conflicting or insufficient data."},{"id":"source_3","type":"source","study":"The Effect of Calcium Supplementation on Body Weight Before and During Pregnancy in Women Enrolled in the WHO Calcium and Preeclampsia Trial","year":2020,"doi":"10.1177/0379572120944671","url":"https://doi.org/10.1177/0379572120944671","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Cormick 2020","excerpt":"INTRODUCTION: Obesity is a major and challenging public health problem. The aim of this substudy is to evaluate the effect of calcium supplementation on body weight in women recruited in the Calcium and Preeclampsia trial. METHODS: Women were recruited before pregnancy and randomized to receive a calcium supplement containing 500 mg of elemental calcium or placebo until 20 weeks' gestation; all women received 1.5 g from 20 weeks until delivery. RESULTS: A total of 630 women conceived during the study, 322 allocated to calcium and 308 to placebo. Among these, 230 allocated to calcium and 227 allocated to placebo had information on body weight at baseline and at 8 weeks' gestation. During the study period, women allocated to calcium had a mean weight increase of 1.1 (SD ±5.5) kg, whereas those allocated to placebo had a mean increase of 1.5 (SD ±6.1) kg, a mean difference of 0.4 kg (95% -0.4 (-1.4 to 0.6); P = .408). Women classified as obese at the start of the trial had a lower body weight gain at 8 weeks' gestation (1.0 kg; 95% CI: -3.2 to 1.2; P = .330) and at 32 weeks' gestation (2.1 kg; 95% CI: 5.6-1.3; P = .225) if they received calcium as compared to placebo."},{"id":"source_4","type":"source","study":"Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis","year":2020,"doi":"10.1007/s10654-020-00710-8","url":"https://doi.org/10.1007/s10654-020-00710-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Pana 2020","excerpt":"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)]."},{"id":"source_5","type":"source","study":"The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials","year":2022,"doi":"10.7554/eLife.79002","url":"https://doi.org/10.7554/eLife.79002","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Liu 2022","excerpt":"BACKGROUND: The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years). METHODS: This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old. RESULTS: This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0."},{"id":"source_6","type":"source","study":"The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: A randomized placebo-controlled study","year":2021,"doi":"10.1016/j.preghy.2020.11.012","url":"https://doi.org/10.1016/j.preghy.2020.11.012","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Hofmeyr 2021","excerpt":"BACKGROUND: Low dietary calcium is associated with the hypertensive disorders of pregnancy, and evidence suggests that the risks associated with pre-eclampsia are reduced by calcium supplementation. In the general (non-pregnant) population, low dietary calcium intake is associated with hypertension with inconsistent evidence that calcium supplementation may reduce blood pressure. Women with pre-eclampsia are also at risk of hypertension later in life. An exploratory sub-study among early participants enrolled in the WHO long-term calcium supplementation in women at high risk of pre-eclampsia (CAP) study reported a trend to more blood pressure reduction with calcium in non-pregnant women with previous severe as opposed to non-severe pre-eclampsia. The current study reports the effects of low-dose calcium supplementation in non-pregnant women in the complete trial cohort. METHODS: The CAP Study was a multi-country randomized, double-blind placebo-controlled clinical trial to test the hypothesis that calcium deficiency may play a role in the genesis of pre-eclampsia in early pregnancy."},{"id":"source_7","type":"source","study":"Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia","year":2024,"doi":"10.1186/s12884-023-06235-8","url":"https://doi.org/10.1186/s12884-023-06235-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Pitilin 2024","excerpt":"BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-ɣ presented lower values in the calcium 1,500 mg/day group (p < 0.005)."},{"id":"source_8","type":"source","study":"The joint effect of energy reduction with calcium supplementation on the risk factors of type 2 diabetes in the overweight population: a two-year randomized controlled trial","year":2021,"doi":"10.18632/aging.202485","url":"https://doi.org/10.18632/aging.202485","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Wei 2021","excerpt":"Both excessive energy intake and low calcium intake are inversely associated with the aging-related diseases, particularly for type 2 diabetes mellitus(T2DM). This study examined whether energy reduction coupled with calcium supplementation aided in the prevention of T2DM among the overweight population. A randomized controlled trial(RCT) of 1021 overweight participants was performed, in which participants were randomly assigned to 4 groups: 1) energy-reduction group(ERG), 2) calcium supplementation group(CSG), 3) energy-reduction with calcium supplementation group(ER-CSG), 4) control group(CG). Nutritional habits, anthropometric and diabetes-related indicators were measured at baseline and each follow-up time. To analyze the separate effects of dietary energy reduction and calcium supplementation, ERG and ER-CSG were integrated into ERGs. Similarly, CSG and ER-CSG were integrated into CSGs. Compared to the non-energy-reduction groups(NERGs), ERGs had lower values of ΔBMI(-0.9kg/m 2 ), ΔFSG (-0.34mmol/L), ΔHbA1c(0.16%), and ΔHOMA-IR(-0.13), and higher value of ΔGutt index(-5.82). Compared to the non-calcium supplementation groups(NCSGs), the ΔGutt index(-5."},{"id":"source_9","type":"source","study":"Effects of maternal calcium supplementation on offspring blood pressure and growth in childhood and adolescence in a population with a low-calcium intake: follow-up study of a randomized controlled trial","year":2024,"doi":"10.1016/j.ajcnut.2024.02.025","url":"https://doi.org/10.1016/j.ajcnut.2024.02.025","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Prentice 2024","excerpt":"BACKGROUND: The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake. OBJECTIVES: The purpose of this study was to investigate whether pregnancy calcium supplementation affects offspring blood pressure and growth in The Gambia where calcium intakes are low (300-400 mg/d). METHODS: Follow-up of offspring born during a randomized controlled trial of pregnancy calcium supplementation (ISRCTN96502494, 1996-2000) in which mothers were randomly assigned to 1500 mg Ca/d (Ca) or placebo (P) from 20 wk pregnancy to delivery. Offspring were enrolled at age 3 y in studies where blood pressure and anthropometry were measured under standardized conditions at approximately 2-yearly intervals. Mean blood pressure and growth curves were fitted for females and males separately, using the longitudinal SuperImposition by Translation and Rotation (SITAR) mixed effects model. This generates 3 individual-specific random effects: size, timing, and intensity, reflecting differences in size, age at peak velocity, and peak velocity through puberty relative to the mean curve, respectively."},{"id":"source_10","type":"source","study":"Effects of Lemon Beverage Containing Citric Acid with Calcium Supplementation on Bone Metabolism and Mineral Density in Postmenopausal Women: Double-Blind 11-Month Intervention Study","year":2021,"doi":"10.1155/2021/8824753","url":"https://doi.org/10.1155/2021/8824753","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Ikeda 2021","excerpt":"A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) supplementation that makes use of the chelating action of citric acid. Comprehensive evaluations of bone were performed by assessments of bone mineral density (BMD) and biomarkers related to bone turnover. Seventy-nine postmenopausal women were enrolled and asked to participate in an 11-month continuous intake of the test beverages. The subjects were divided into three groups: those who consumed a lemon beverage containing citric acid with Ca supplementation (LECA group), those who consumed a lemon beverage containing citric acid without Ca supplementation (LE group), and those who consumed no test beverage (control group). Using a double-blind protocol, subjects in the LECA and LE groups consumed one bottle containing 290 mL of the test beverage each day. The ratio of change in BMD after 11 months was significantly higher in the LECA group as compared to the control and LE groups."},{"id":"source_11","type":"source","study":"EFFECTS OF CALCIUM SUPPLEMENTATION ON THE RISK OF FRACTURE IN OLDER ADULTS","year":2025,"doi":"10.1590/1413-785220253306e284103","url":"https://doi.org/10.1590/1413-785220253306e284103","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Li 2025","excerpt":"To explore the effect of calcium supplementation on the risk of fractures at various sites in older adults based on randomized controlled trials (RCTs). PubMed, Embase, and the Cochrane Library were systematically searched for eligible RCTs from their inception until May 2023. The included trials investigated the effect of calcium supplementation on the risk of fracture in individuals aged 50 years or above, regardless of the use or nonuse of vitamin D. The primary and secondary outcome measures were total, vertebral, nonvertebral, and hip fractures. Twenty-three RCTs involving 70,837 individuals were enrolled. Calcium supplementation demonstrated a significant reduction in the risk of total (RR: 0.93; 95% CI: 0.88-0.99; P=0.019) and nonvertebral (RR: 0.93; 95% CI: 0.87-0.99; P=0.023) fractures. No significant differences were observed in vertebral (RR: 0.87; 95% CI: 0.75-1.01; P=0.074) and hip (RR: 0.90; 95% CI: 0.73-1.12; P=0.355) fractures between calcium and placebo or no treatment. Calcium dose influenced total fracture risk (P=0.008), while history of fracture (P=0.044), calcium dose (P=0.041), and follow-up duration (P=0.031) affected nonvertebral fracture risk."},{"id":"source_12","type":"source","study":"Association Between Calcium Supplementation and Recurrence of Cardiovascular Events in Patients With Cardiovascular Disease: A Population‐Based Cohort Study","year":2026,"doi":"10.1161/JAHA.125.047455","url":"https://doi.org/10.1161/JAHA.125.047455","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Zhang 2026","excerpt":"BACKGROUND: The cardiovascular safety of calcium supplements in individuals with major cardiovascular disease (CVD) remains unclear. This study investigated the association between calcium supplementation and the risk of CVD recurrence in patients with established CVD. METHODS: A retrospective population-based study was conducted in Hong Kong of individuals aged ≥40 years newly diagnosed with CVD from January 1, 2006, to December 31, 2015. The treatment group consisted of patients with CVD prescribed calcium supplements, while the control group consisted of those who never prescribed calcium supplements from January 1, 2005, to December 31, 2020. Propensity score matching and Cox proportional hazard models were adopted to balance the baseline characteristics and estimate hazards ratios (HRs) for CVD recurrence. RESULTS: The matched cohort included 17 720 patients with CVD in each arm. Calcium supplementation was associated with an increased risk of recurrence of adverse CVD events (HR, 1.10 [95% CI, 1.07-1.14]) and CVD-related hospitalization or accident and emergency department attendance (HR, 1.16 [95% CI, 1.13-1.20])."},{"id":"source_13","type":"source","study":"The Positive and Negative Effects of Calcium Supplementation on Mortality in Septic ICU Patients Depend on Disease Severity: A Retrospective Study from the MIMIC-III","year":2022,"doi":"10.1155/2022/2520695","url":"https://doi.org/10.1155/2022/2520695","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"He 2022","excerpt":"BACKGROUND: Calcium administration in septic patients with hypocalcemia is a controversial issue. The present study preliminarily investigated the effects of calcium supplementation on the length of hospitalization and mortality in septic ICU patients with different severities of hypocalcemia and disease. METHOD: A total of 5761 eligible septic patients, including 2689 who received calcium supplementation and 3072 who did not receive calcium supplementation, were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The cofounding covariates between the calcium supplement and nonsupplement groups were balanced using the propensity score matching model. We compared the length of stay (LOS) in the ICU and hospital with 28-day and hospital mortality and stratified the analysis according to the sequential organ failure assessment (SOFA) score and ionized calcium (iCa) at the first ICU admission in the matched groups. RESULTS: The results showed that iCa at the first ICU admission was associated with mortality in sepsis patients (HR: 0.421; 95% CI: 0.211∼0.837), but the lowest mortality rate was observed in patients with mild hypocalcemia."},{"id":"source_14","type":"source","study":"Effects of calcium supplementation on the prevention of preeclampsia: an umbrella review of systematic reviews and meta-analyses","year":2025,"doi":"10.3389/fmed.2025.1434416","url":"https://doi.org/10.3389/fmed.2025.1434416","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Kumsa 2025","excerpt":"BACKGROUND: Preeclampsia is the leading cause of maternal and fetal morbidity and mortality. Calcium supplementation has been considered a potential intervention to reduce the risk of preeclampsia. This umbrella review aims to summarize the effects of calcium supplementation in the prevention of preeclampsia based on existing systematic reviews and meta-analyses studies. METHODS: A systematic search of electronic databases, such as MEDLINE, Web of Science, SCOPUS, and the Cochrane Library, was conducted from inception to 30 December 2023. The methodological quality of the included studies was assessed using the revised version of the Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool. A random-effects model was used to estimate the effect of calcium supplementation on preeclampsia. Heterogeneity among included studies and publication bias were assessed using the I 2 statistic and the Egger's test, respectively. RESULTS: Calcium supplementation reduced the risk of preeclampsia by 47% (RR: 0.53, 95% CI: 0.42, 0.68) with a considerable level of heterogeneity (I 2 = 84.39%)."},{"id":"source_15","type":"source","study":"Increased Reproductive Output and Telomere Shortening Following Calcium Supplementation in a Wild Songbird","year":2024,"doi":"10.1002/ece3.70483","url":"https://doi.org/10.1002/ece3.70483","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Rodriguez 2024","excerpt":"Life history theory predicts increased parental investment comes with fitness costs, often expressed as negative effects on survival and future reproduction. To better understand the costs of reproduction and life history trade-offs, we evaluated calcium supplementation at a high-elevation site in Colorado as a novel approach to experimentally alter reproductive investment in nesting female Tachycineta bicolor (tree swallow). Calcium is a nutrient critical to avian reproduction as the intake of natural calcium is essential for egg production, embryo development, and nestling growth. Altering calcium availability exclusively during the breeding season allowed examination of individual biological responses to experimental modification of reproduction, as well as the reproductive costs associated with egg production and laying an entire clutch. As a functional endpoint and proxy for fitness and longevity, telomere length was measured at the beginning and end of each breeding season. Telomeres-protective \"caps\" at the ends of chromosomes-have been shown to shorten with aging and a variety of stressors, including higher reproductive output."},{"id":"source_16","type":"source","study":"Effects of calcium supplementation to resuscitation fluids in endurance horses: A randomized, blinded, clinical trial","year":2023,"doi":"10.1111/jvim.16715","url":"https://doi.org/10.1111/jvim.16715","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Fielding 2023","excerpt":"BACKGROUND: The addition of calcium to resuscitation fluids is a common practice in horses, but studies evaluating the effects of calcium supplementation are limited. In healthy horses, decreases in heart rate and changes in serum electrolyte concentrations have been reported. HYPOTHESIS: Calcium gluconate administration at a rate of 0.4 mg/kg/min to eliminated endurance horses with metabolic problems will affect heart rate, gastrointestinal sounds, and serum electrolyte concentrations. ANIMALS: Endurance horses eliminated from the Tevis Cup 100-mile (160 km) endurance ride for metabolic problems and requiring IV fluid therapy were eligible. METHODS: Sixteen horses were randomly assigned to receive 0.4 mg/kg/min of calcium (23% calcium gluconate solution) over 1 hour diluted in 10 L of a non-calcium containing isotonic crystalloid (CAL group) or 10 L of a non-calcium containing isotonic crystalloid (CON group). Staff members administering the fluids were blinded to treatment group. Blood samples were collected and physical examinations performed before and after treatment. Heart rates were recorded every 15 min during fluid administration."},{"id":"source_17","type":"source","study":"Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania","year":2021,"doi":"10.1186/s13063-021-05811-7","url":"https://doi.org/10.1186/s13063-021-05811-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"protocol","cited_as":"Dwarkanath 2021","excerpt":"BACKGROUND: Hypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500-2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (< 1000 mg elemental calcium/day) during pregnancy have also shown similar reductions in the risk of preeclampsia; however, no trials to date have directly compared low-dose to the standard high-dose calcium supplementation. Our objective is to assess the non-inferiority of low-dose as compared to standard high-dose calcium supplementation in pregnancy. METHODS/DESIGN: We will conduct two independent trials in Bangalore, India (n = 11,000 pregnancies), and Dar es Salaam, Tanzania (n = 11,000 pregnancies)."},{"id":"source_18","type":"source","study":"Calcium Supplementation in Pregnancy: A Systematic Review of Clinical Studies","year":2025,"doi":"10.3390/medicina61071195","url":"https://doi.org/10.3390/medicina61071195","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Gerede 2025","excerpt":"Background and Objectives : Calcium is an essential mineral that plays a vital role in fetal development and maternal health during pregnancy. The World Health Organization recommends a daily calcium intake of 1.5-2 g for pregnant adult women. Calcium deficiency during gestation may lead to complications, such as gestational hypertension, preeclampsia, loss of bone mineral density, impaired fetal development, and other adverse pregnancy outcomes. The aim of the present review is to evaluate the current clinical evidence on calcium intake during pregnancy. Methods : The present systematic review was conducted according to the PRISMA 2020 statement by searching two major databases, PubMed and Mendeley. The study protocol was registered in the Open Science Framework (DOI: osf.io/rvj7z). Inclusion criteria were clinical trials on calcium supplementation during pregnancy. Exclusion criteria were clinical guidelines, reviews, case reports, case series, letters, and commentaries. The Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies."},{"id":"source_19","type":"source","study":"Calcium supplementation for prevention of pre-eclampsia in high-risk women: study protocol for a randomised triple-blind placebo-controlled trial (CaPE)","year":2026,"doi":"10.1186/s13063-026-09513-w","url":"https://doi.org/10.1186/s13063-026-09513-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"protocol","cited_as":"Meher 2026","excerpt":"BACKGROUND: Pre-eclampsia is a multisystem disorder affecting 2.8% of pregnancies in the UK. It usually presents after 20-week gestation with new-onset high blood pressure and proteinuria. Complications include eclampsia, stroke, and HELLP syndrome for the mother and preterm birth, fetal growth restriction, and stillbirth for the baby. Delivery is the only definitive cure, with antenatal care focusing on early detection and management of complications and optimising timing of delivery. Previous studies have shown calcium supplementation may reduce the risk of pre-eclampsia, but findings are driven by large effects seen in small trials that have not been replicated in larger trials. Subgroup analysis suggests benefits may only be seen in women with low dietary calcium intake, so findings may not be applicable to populations with adequate dietary calcium. Although the largest benefits appear to be in high-risk women, data are very limited, with no large trials conducted."},{"id":"source_20","type":"source","study":"Different Doses of Calcium Supplementation to Prevent Gestational Hypertension and Pre-Eclampsia: A Systematic Review and Network Meta-Analysis","year":2022,"doi":"10.3389/fnut.2021.795667","url":"https://doi.org/10.3389/fnut.2021.795667","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Chen 2022","excerpt":"OBJECTIVE: Calcium supplementation can prevent gestational hypertension and pre-eclampsia. However, besides the non-consensus of existing studies, there is a lack of evidence regarding the optimal dosing of calcium. METHOD: Eight electronic databases, namely, the Cochrane Library, PUBMED, Web of Science, EMBASE, WANGFANG, VIP, CBM, and CNKI, were searched. The studies were retrieved from inception to July 13, 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. In particular, the calcium supplementation doses were divided into three groups, namely, the high-dose (≥1.5 g), medium-dose (1.0-1.49 g), and the low-dose group (<1.0 g). The participants were also divided into high-risk and low-risk groups, according to the risk of developing gestational hypertension and pre-eclampsia. RESULTS AND DISCUSSION: A total of 48 studies were incorporated into the final analyses."},{"id":"source_21","type":"source","study":"Vitamin D supplementation and risk of stroke: A meta-analysis of randomized controlled trials","year":2022,"doi":"10.3389/fneur.2022.970111","url":"https://doi.org/10.3389/fneur.2022.970111","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Fu 2022","excerpt":"BACKGROUND: Previous observational studies have supported the hypothesis that vitamin D supplementation protects against stroke. However, several current intervention studies contradict this observation. Therefore, we conducted a meta-analysis to investigate further the association between vitamin D supplementation and the risk of stroke. METHODS: This meta-analysis was conducted in accordance with the PRISMA statement and included all the randomized controlled trials (RCTs) that analyzed the relationship between vitamin D supplementation and the risk of stroke. A literature search strategy was established, and the following Medical Search Terms (MeSH) were used: \"vitamin D,\" \"Calcitriol,\" \"Calcifediol,\" \"Cholecalciferol,\" \"25-Hydroxyvitamin D 2,\" \"ergocalciferols,\" \"stroke,\" and stroke-derived terms. We searched for articles published before January 2022 in several databases, namely, PubMed, Web of Science, EMBASE, and The Cochrane Library. We also reviewed references included in relevant published meta-analyses and searched the http://www.ClinicalTrials.gov website for additional RCTs. The Q test and I 2 were utilized to assess the degree of heterogeneity among the studies."},{"id":"source_22","type":"source","study":"Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy","year":2024,"doi":"10.1056/NEJMoa2307212","url":"https://doi.org/10.1056/NEJMoa2307212","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Dwarkanath 2024","excerpt":"BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials."},{"id":"source_23","type":"source","study":"Factors affecting the implementation of calcium supplementation strategies during pregnancy to prevent pre-eclampsia: a mixed-methods systematic review","year":2023,"doi":"10.1136/bmjopen-2022-070677","url":"https://doi.org/10.1136/bmjopen-2022-070677","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Cormick 2023","excerpt":"OBJECTIVES: Daily calcium supplements are recommended for pregnant women from 20 weeks' gestation to prevent pre-eclampsia in populations with low dietary calcium intake. We aimed to improve understanding of barriers and facilitators for calcium supplement intake during pregnancy to prevent pre-eclampsia. DESIGN: Mixed-method systematic review, with confidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations-Confidence in the Evidence from Reviews of Qualitative research approach. DATA SOURCES: MEDLINE and EMBASE (via Ovid), CINAHL and Global Health (via EBSCO) and grey literature databases were searched up to 17 September 2022. ELIGIBILITY CRITERIA: We included primary qualitative, quantitative and mixed-methods studies reporting implementation or use of calcium supplements during pregnancy, excluding calcium fortification and non-primary studies. No restrictions were imposed on settings, language or publication date. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias."},{"id":"source_24","type":"source","study":"Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis","year":2020,"doi":"10.1007/s12603-020-1551-9","url":"https://doi.org/10.1007/s12603-020-1551-9","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Zhang 2020","excerpt":"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."},{"id":"source_25","type":"source","study":"The effect of calcium supplementation on calcium and bone metabolism during load carriage in women: protocol for a randomised controlled crossover trial","year":2023,"doi":"10.1186/s12891-023-06600-w","url":"https://doi.org/10.1186/s12891-023-06600-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Coombs 2023","excerpt":"BACKGROUND: Military field exercises are characterised by high volumes of exercise and prolonged periods of load carriage. Exercise can decrease circulating serum calcium and increase parathyroid hormone and bone resorption. These disturbances to calcium and bone metabolism can be attenuated with calcium supplementation immediately before exercise. This randomised crossover trial will investigate the effect of calcium supplementation on calcium and bone metabolism, and bone mineral balance, during load carriage exercise in women. METHODS: Thirty women (eumenorrheic or using the combined oral contraceptive pill, intrauterine system, or intrauterine device) will complete two experimental testing sessions either with, or without, a calcium supplement (1000 mg). Each experimental testing session will involve one 120 min session of load carriage exercise carrying 20 kg. Venous blood samples will be taken and analysed for biochemical markers of bone resorption and formation, calcium metabolism, and endocrine function. Urine will be collected pre- and post-load carriage to measure calcium isotopes for the calculation of bone calcium balance."},{"id":"source_26","type":"source","study":"Vitamin D and calcium supplementation in women undergoing pharmacological management for postmenopausal osteoporosis: a level I of evidence systematic review","year":2025,"doi":"10.1186/s40001-025-02412-x","url":"https://doi.org/10.1186/s40001-025-02412-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Migliorini 2025","excerpt":"The present systematic review investigates whether different doses of vitamin D and calcium supplementation in women with postmenopausal osteoporosis undergoing antiresorptive therapy have an association with BMD (spine, hip, femur neck), serum markers of osteoporosis (bone-ALP, NTX, CTX), the rate of pathological vertebral and non-vertebral fractures, adverse events, and mortality. This systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Scopus databases were accessed in September 2024. All randomised clinical trials (RCTs) comparing two or more treatments for postmenopausal osteoporosis supplemented with vitamin D and/or calcium were accessed. Only studies that indicated daily vitamin D and/or calcium supplementation doses were accessed. Data from 37 RCTs (43,397 patients) were retrieved. Patients received a mean of 833.6 ± 224.0 mg and 92.8 ± 228.7 UI of calcium and vitamin D supplementation, respectively. The mean length of the follow-up was 25.8 ± 13.3 months. The mean age of the patients was 66.4 ± 5.6 years, and the mean BMI was 25.2 ± 1.6 kg/m 2 ."},{"id":"source_27","type":"source","study":"Effectiveness of calcium supplementation in the prevention of gestational hypertension: A systematic review and meta-analysis of randomised controlled trials.","year":2024,"doi":"10.1016/j.preghy.2024.101174","url":"https://doi.org/10.1016/j.preghy.2024.101174","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Zhu 2024","excerpt":"BACKGROUND: Gestational hypertension and related disorders, such as preeclampsia, pose significant risks to maternal and foetal health. Calcium supplementation has been proposed as a preventive measure, but its effectiveness remains debated. This review assess the impact of calcium supplementation in prevention of gestational hypertension. METHODS: A comprehensive literature search was conducted across multiple databases, including Scopus, EMBASE, PubMed, Web of Science, CINAHL, Cochrane CENTRAL, from inception to July 2024. Eligibility criteria included studies involving pregnant women at risk of gestational hypertension, comparing calcium supplementation to control group, and reporting on outcomes such as preeclampsia, pregnancy-induced hypertension, HELLP syndrome, preterm birth, and maternal mortality. Data were analysed using a random-effects inverse-variance model to calculate pooled risk ratios (RRs) and assess heterogeneity using Cochran's Q and I2 statistics. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: 22 studies with 39,270 individuals were included. Most studies had higher risk of bias."},{"id":"source_28","type":"source","study":"Calcium supplementation for people with overweight or obesity.","year":2024,"doi":"10.1002/14651858.cd012268.pub2","url":"https://doi.org/10.1002/14651858.cd012268.pub2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Cormick 2024","excerpt":"BACKGROUND: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months."},{"id":"source_29","type":"source","study":"The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial.","year":2022,"doi":"10.1080/1028415x.2019.1707396","url":"https://doi.org/10.1080/1028415x.2019.1707396","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Amini 2022","excerpt":"Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD. Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured. Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p = 0.008)."},{"id":"source_30","type":"source","study":"Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial","year":2014,"doi":"10.1371/journal.pone.0109607","url":"https://doi.org/10.1371/journal.pone.0109607","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Gagnon 2014","excerpt":"OBJECTIVES: To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. DESIGN: 6-month randomized, placebo-controlled trial. PARTICIPANTS: Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). INTERVENTION: Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000-6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. MEASUREMENTS: Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. RESULTS: Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D."},{"id":"source_31","type":"source","study":"Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial","year":2014,"doi":"10.1590/1414-431X20143629","url":"https://doi.org/10.1590/1414-431X20143629","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Souza 2014","excerpt":"Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80."},{"id":"source_32","type":"source","study":"Calcium Supplementation Increases Blood Creatinine Concentration in a Randomized Controlled Trial","year":2014,"doi":"10.1371/journal.pone.0108094","url":"https://doi.org/10.1371/journal.pone.0108094","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barry 2014","excerpt":"BACKGROUND: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied. METHODS: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004-2013 at 11 clinical centers in the United States. Healthy participants (N = 1,675) aged 45-75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations. RESULTS: After one year of treatment, blood creatinine was 0.013±0.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03)."},{"id":"source_33","type":"source","study":"Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries","year":2011,"doi":"10.1186/1471-2458-11-S3-S18","url":"https://doi.org/10.1186/1471-2458-11-S3-S18","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Imdad 2011","excerpt":"BACKGROUND: Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. METHODS: A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia."},{"id":"source_34","type":"source","study":"Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy","year":2018,"doi":"10.3390/nu10030294","url":"https://doi.org/10.3390/nu10030294","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"OCallaghan 2018","excerpt":"This narrative systematic review evaluates growing evidence of an association between low maternal vitamin D status and increased risk of hypertensive disorders. The inclusion of interventional, observational, and dietary studies on vitamin D and all hypertensive disorders of pregnancy is a novel aspect of this review, providing a unique contribution to an intensively-researched area that still lacks a definitive conclusion. To date, trial evidence supports a protective effect of combined vitamin D and calcium supplementation against preeclampsia. Conflicting data for an association of vitamin D with gestational hypertensive disorders in observational studies arises from a number of sources, including large heterogeneity between study designs, lack of adherence to standardized perinatal outcome definitions, variable quality of analytical data for 25-hydroxyvitamin D (25(OH)D), and inconsistent data reporting of vitamin D status. While evidence does appear to lean towards an increased risk of gestational hypertensive disorders at 25(OH)D concentrations <50 nmol/L, caution should be exercised with dosing in trials, given the lack of data on long-term safety."},{"id":"source_35","type":"source","study":"Risk of Ischemic Stroke Associated With Calcium Supplements With or Without Vitamin D: A Nested Case‐Control Study","year":2017,"doi":"10.1161/JAHA.117.005795","url":"https://doi.org/10.1161/JAHA.117.005795","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Abajo 2017","excerpt":"BACKGROUND: There is controversy surrounding the risk of ischemic stroke associated with the use of calcium supplements either in monotherapy or in combination with vitamin D. METHODS AND RESULTS: A nested case-control study was performed with patients aged 40 to 89 years old, among whom a total of 2690 patients had a first episode of nonfatal ischemic stroke and for which 19 538 controls were randomly selected from the source population and frequency-matched with cases for age, sex, and calendar year. Logistic regression provided the odds ratios while adjusting for confounding factors. A sensitivity analysis was performed by restricting to patients who were new users of calcium supplements as either monotherapy or with vitamin D. Calcium supplementation with vitamin D was not associated with an increased risk of ischemic stroke (odds ratio 0.85; 95% confidence interval, 0.67-1.08) in the population as a whole or under any of the conditions examined (dose, duration, background cardiovascular risk, sex, or age). Calcium supplement monotherapy was not associated with an increased risk in the population as a whole (odds ratio 1.18; 95% confidence interval, 0.86-1."},{"id":"source_36","type":"source","study":"Effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in vitamin D-deficient Asian Indians: a randomized, controlled trial.","year":2010,"doi":"10.1111/j.1365-2265.2010.03816.x","url":"https://doi.org/10.1111/j.1365-2265.2010.03816.x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Gupta 2010","excerpt":"CONTEXT: Vitamin D deficiency is prevalent worldwide. Vitamin D supplementation has shown variable effect on skeletal muscle strength in the elderly with hypovitaminosis D. There is a paucity of similar data in young individuals. OBJECTIVE: To study the effect of cholecalciferol and calcium supplementation on muscle strength and energy metabolism in young individuals. SUBJECTS: Forty healthy volunteers (24 M/16 F, mean age (SD) 31.5 ± 5.0 year) with hypovitaminosis D were randomized to either oral cholecalciferol (60,000 IU D3/week for 8 weeks followed by 60,000 IU/month for 4 months) with 1 g of elemental calcium daily or dual placebos for 6 months. MEASUREMENTS: Handgrip and gastro-soleus dynamometry, pinch-grip strength, respiratory pressures, 6-min walk-test and muscle energy metabolism on (31) P magnetic resonance spectroscopy were assessed at baseline and after 6 months. RESULTS: The mean serum 25(OH)D in the supplemented and placebo groups at baseline, two and 6 months were 25.4 ± 9.9, 94.5 ± 53.8 and 56.0 ± 17.0 nm, and 21.1 ± 9.4, 32.8 ± 14.4 and 29.7 ± 15.0 nm, respectively. 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