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Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy.
Hofmeyr, GJ, Manyame, S, Medley, N, Williams, MJ
The Cochrane database of systematic reviews. 2019;(9):CD011192
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Abstract
BACKGROUND The hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) has added benefit. Such evidence could count towards justification of population-level interventions to improve dietary calcium intake, including fortification of staple foods with calcium, especially in contexts where dietary calcium intake is known to be inadequate. This is an update of a review first published in 2017. OBJECTIVES To determine the effect of calcium supplementation, given before or early in pregnancy and for at least the first half of pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and fetal and neonatal outcomes. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Trials Register (31 July 2018), PubMed (13 July 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 31 July 2018), and reference lists of retrieved studies. SELECTION CRITERIA Eligible studies were randomised controlled trials (RCT) of calcium supplementation, including women not yet pregnant, or women in early pregnancy. Cluster-RCTs, quasi-RCTs, and trials published as abstracts were eligible, but we did not identify any. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. They assessed the quality of the evidence for key outcomes using the GRADE approach. MAIN RESULTS Calcium versus placeboWe included one study (1355 women), which took place across multiple hospital sites in Argentina, South Africa, and Zimbabwe. Most analyses were conducted only on 633 women from this group who were known to have conceived, or on 579 who reached 20 weeks' gestation; the trial was at moderate risk of bias due to high attrition rates pre-conception. Non-pregnant women with previous pre-eclampsia received either calcium 500 mg daily or placebo, from enrolment until 20 weeks' gestation. All participants received calcium 1.5 g daily from 20 weeks until birth.Primary outcomes: calcium supplementation commencing before conception may make little or no difference to the risk of pre-eclampsia (69/296 versus 82/283, risk ratio (RR) 0.80, 95% confidence interval (CI) 0.61 to 1.06; low-quality evidence). For pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age, calcium may slightly reduce the risk of this composite outcome, however the 95% CI met the line of no effect (RR 0.82, 95% CI 0.66 to 1.00; low-quality evidence). Supplementation may make little or no difference to the severe maternal morbidity and mortality index (RR 0.93, 95% CI 0.68 to 1.26; low-quality evidence), pregnancy loss or stillbirth at any gestational age (RR 0.83, 95% CI 0.61 to 1,14; low-quality evidence), or caesarean section (RR 1.11, 95% CI 0.96 to 1,28; low-quality evidence).Calcium supplementation may make little or no difference to the following secondary outcomes: birthweight < 2500 g (RR 1.00, 95% CI 0.76 to 1.30; low-quality evidence), preterm birth < 37 weeks (RR 0.90, 95% CI 0.74 to 1.10), early preterm birth < 32 weeks (RR 0.79, 95% CI 0.56 to 1.12), and pregnancy loss, stillbirth or neonatal death before discharge (RR 0.82, 95% CI 0.61 to 1.10; low-quality evidence), no conception, gestational hypertension, gestational proteinuria, severe gestational hypertension, severe pre-eclampsia, severe pre-eclamptic complications index. There was no clear evidence on whether or not calcium might make a difference to perinatal death, or neonatal intensive care unit admission for > 24h, or both (RR 1.11, 95% CI 0.77 to 1.60; low-quality evidence).It is unclear what impact calcium supplementation has on Apgar score < 7 at five minutes (RR 0.43, 95% CI 0.15 to 1.21; very low-quality evidence), stillbirth, early onset pre-eclampsia, eclampsia, placental abruption, intensive care unit admission > 24 hours, maternal death, hospital stay > 7 days from birth, and pregnancy loss before 20 weeks' gestation. AUTHORS' CONCLUSIONS The single included study suggested that calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. Therefore, current evidence neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy.To determine the overall benefit of calcium supplementation commenced before or in early pregnancy, the effects found in the study of calcium supplementation limited to the first half of pregnancy need to be added to the known benefits of calcium supplementation in the second half of pregnancy.Further research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.
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Dietary calcium intake and the risk of metabolic syndrome: evidence from observational studies.
Cheng, L, Hu, D, Jiang, W
Public health nutrition. 2019;(11):2055-2062
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OBJECTIVE Epidemiological investigations evaluating the association of dietary Ca intake with metabolic syndrome (MetS) risk have yielded controversial results. Therefore, a meta-analysis was conducted to quantitatively summarize the association between dietary Ca intake and the risk of MetS. DESIGN PubMed, Embase and Web of Science were searched for relevant articles published up to October 2018. The pooled OR and 95 % CI were calculated with a random-effects model. SETTING Meta-analysis.ParticipantsNine cross-sectional studies. RESULTS A total of nine articles with fifteen studies for dietary Ca intake were finally included in the meta-analysis. The combined OR with 95 % CI of MetS for the highest v. lowest category of dietary Ca intake was 0·80 (95 % CI 0·70, 0·91). For dose-response analysis, a non-linear relationship was found between dietary intake of Ca and risk of MetS (P non-linearity<0·001). The threshold for dietary Ca intake was 280 mg/d (OR=0·87; 95 % CI 0·82, 0·93), reducing the risk of MetS by 13 %. CONCLUSIONS The present meta-analysis suggests that dietary Ca intake might reduce the risk of MetS, which needs to be further confirmed by larger prospective cohort studies.
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Calcium Intake and Health.
Cormick, G, Belizán, JM
Nutrients. 2019;(7)
Abstract
There are striking inequities in calcium intake between rich and poor populations. Appropriate calcium intake has shown many health benefits, such as reduction of hypertensive disorders of pregnancy, lower blood pressure particularly among young people, prevention of osteoporosis and colorectal adenomas, lower cholesterol values, and lower blood pressure in the progeny of mothers taking sufficient calcium during pregnancy. Studies have refuted some calcium supplementation side effects like damage to the iron status, formation of renal stones and myocardial infarction in older people. Attention should be given to bone resorption in post-partum women after calcium supplementation withdrawal. Mechanisms linking low calcium intake and blood pressure are mediated by parathyroid hormone raise that increases intracellular calcium in vascular smooth muscle cells leading to vasoconstriction. At the population level, an increase of around 400-500 mg/day could reduce the differences in calcium intake between high- and middle-low-income countries. The fortification of food and water seems a possible strategy to reach this goal.
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Vitamin D with calcium supplementation and risk of atrial fibrillation in postmenopausal women.
Boursiquot, BC, Larson, JC, Shalash, OA, Vitolins, MZ, Soliman, EZ, Perez, MV
American heart journal. 2019;:68-78
Abstract
BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia in adults. Although vitamin D deficiency is associated with AF risk factors, retrospective studies of association with AF have shown mixed results. We sought to determine the efficacy of calcium and vitamin D (CaD) supplementation for AF prevention in a randomized trial. METHODS We performed a secondary analysis of the Women's Health Initiative trial on CaD supplementation versus placebo. We linked participants to their Medicare claims to ascertain incident AF. RESULTS Among 16,801 included participants, there were 1,453 (8.6%) cases of incident AF over an average of 4.5 years, at an average rate of 19.9 events per 1,000 person-years. We found no significant difference in incident AF rates between the CaD and placebo arms (hazard ratio 1.02 for CaD vs placebo, 95% CI 0.92-1.13). After multivariate adjustment, there was no significant association between baseline 25-hydroxyvitamin D serum levels and incident AF (hazard ratio 0.92 for lowest subgroup vs highest subgroup, 95% CI 0.66-1.28). CONCLUSIONS We present the first analysis of a large randomized trial of daily vitamin D supplementation for AF prevention. We found that CaD had no effect on incidence of AF in Women's Health Initiative CaD trial participants. We also found that baseline serum 25-hydroxyvitamin D level was not predictive of long-term incident AF risk.
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The vitamin D and calcium controversy: an update.
Lewis, JR, Sim, M, Daly, RM
Current opinion in rheumatology. 2019;(2):91-97
Abstract
PURPOSE OF REVIEW Calcium and vitamin D supplementation is widely recommended for prevention of falls and fracture, particularly in the elderly where calcium intakes and vitamin D levels are often inadequate. A number of meta-analyses have questioned the benefits of untargeted or 'holistic' supplementation for falls and fracture, and raised the possibility of adverse cardiovascular effects. This review provides an update on these controversies. RECENT FINDINGS Recent advances have largely centred around new trials of vitamin D and meta-analyses of published trials and observational studies. These articles have identified holistic vitamin D supplementation with or without calcium is unlikely to be an effective primary prevention strategy for falls or fracture. There has also been high-quality evidence that vitamin D, daily or as a bolus, does not reduce the risk of cardiovascular events. SUMMARY The benefits of vitamin D and calcium supplements for holistic fall and fracture prevention remain uncertain. Recent evidence supports the concept that high-dose vitamin D has adverse musculoskeletal effects. Future studies should focus on moderate daily doses. Finally, there remain inconsistent findings for adverse cardiovascular effects of calcium supplements with or without vitamin D. This uncertainty should be taken into account when evaluating the risk/benefits of supplementation.
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Dietary Calcium Intake and Bone Loss Over 6 Years in Osteopenic Postmenopausal Women.
Bristow, SM, Horne, AM, Gamble, GD, Mihov, B, Stewart, A, Reid, IR
The Journal of clinical endocrinology and metabolism. 2019;(8):3576-3584
Abstract
CONTEXT Calcium intakes are commonly lower than the recommended levels, and increasing calcium intake is often recommended for bone health. OBJECTIVE To determine the relationship between dietary calcium intake and rate of bone loss in older postmenopausal women. PARTICIPANTS Analysis of observational data collected from a randomized controlled trial. Participants were osteopenic (hip T-scores between -1.0 and -2.5) women, aged >65 years, not receiving therapy for osteoporosis nor taking calcium supplements. Women from the total cohort (n = 1994) contributed data to the analysis of calcium intake and bone mineral density (BMD) at baseline, and women from the placebo group (n = 698) contributed data to the analysis of calcium intake and change in BMD. BMD and bone mineral content (BMC) of the spine, total hip, femoral neck, and total body were measured three times over 6 years. RESULTS Mean calcium intake was 886 mg/day. Baseline BMDs were not related to quintile of calcium intake at any site, before or after adjustment for baseline age, height, weight, physical activity, alcohol intake, smoking status, and past hormone replacement use. There was no relationship between bone loss and quintile of calcium intake at any site, with or without adjustment for covariables. Total body bone balance (i.e., change in BMC) was unrelated to an individuals' calcium intake (P = 0.99). CONCLUSIONS Postmenopausal bone loss is unrelated to dietary calcium intake. This suggests that strategies to increase calcium intake are unlikely to impact the prevalence of and morbidity from postmenopausal osteoporosis.
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No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial.
Calderwood, AH, Baron, JA, Mott, LA, Ahnen, DJ, Bostick, RM, Figueiredo, JC, Passarelli, MN, Rees, JR, Robertson, DJ, Barry, EL
Cancer prevention research (Philadelphia, Pa.). 2019;(5):295-304
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Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93-1.17) for vitamin D versus no vitamin D; 0.95 (0.84-1.08) for calcium versus no calcium; 1.07 (0.91-1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81-1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.
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Calcium Intake and Survival after Colorectal Cancer Diagnosis.
Yang, W, Ma, Y, Smith-Warner, S, Song, M, Wu, K, Wang, M, Chan, AT, Ogino, S, Fuchs, CS, Poylin, V, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2019;(6):1980-1988
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PURPOSE Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.Experimental Design: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 nonmetastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression. RESULTS Comparing the highest with the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32-0.96; P trend = 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59-1.09; P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with colorectal cancer-specific mortality (HR, 0.67; 95% CI, 0.42-1.06; P trend = 0.047) and all-cause mortality (HR, 0.71; 95% CI, 0.54-0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men. CONCLUSIONS Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer survivors.
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Physical activity modifies the effect of calcium supplements on bone loss in perimenopausal and postmenopausal women: subgroup analysis of a randomized controlled trial.
Nakamura, K, Saito, T, Kobayashi, R, Oshiki, R, Kitamura, K, Watanabe, Y
Archives of osteoporosis. 2019;(1):17
Abstract
UNLABELLED We aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of an RCT. PA may be a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women. PURPOSE Physical exercise can potentially modify bone metabolism. Here we aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of a randomized, double-blind, placebo-controlled trial. METHODS The trial was conducted over the course of 2 years, and participants were 450 healthy women between 50 and 75 years of age who were randomly assigned to three equally-sized (N = 150 each) groups (500 mg calcium, 250 mg calcium, and placebo). Levels of PA at baseline were evaluated by quantifying moderate (4 METs) and vigorous (6 METs) activities based on a 7-day activity recall, and the total MET-hours per week was calculated. Follow-up BMD examinations were conducted 2 years later. Two-year changes in BMD were compared between the intention-to-treat higher PA subgroup (≥ 10 MET-hours/week) and the lower PA subgroup (< 10 MET-hours/week). RESULTS Of the 450 participants, 418 underwent follow-up BMD measurements. Regarding the lower PA subgroup, spinal BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.029 g/cm2, P = 0.042) than in the placebo group (- 0.045 g/cm2), and femoral neck BMD in the 500 mg/day calcium supplement group decreased significantly less (- 0.027 g/cm2, P = 0.049) than in the placebo group (- 0.038 g/cm2). In contrast, changes in neither spinal nor femoral neck BMD significantly differed between the three treatment groups in the higher PA subgroup. CONCLUSIONS PA is a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women with low calcium intake. CLINICAL TRIALS REGISTRY NUMBER UMIN000001176.
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Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism.
Edafe, O, Mech, CE, Balasubramanian, SP
The Cochrane database of systematic reviews. 2019;(5):CD012845
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BACKGROUND Post-surgical hypoparathyroidism is a common complication after thyroid surgery. The incidence is likely to increase given the rising trend in the annual number of thyroid operations being performed. Measures to prevent post-thyroidectomy hypoparathyroidism including different surgical techniques and prophylactic calcium and vitamin D supplements have been extensively studied. The management of post-thyroidectomy hypoparathyroidism however has not been extensively evaluated. Routine use of calcium and vitamin D supplements in the postoperative period may reduce the risk of symptoms, temporary hypocalcaemia and hospital stay. However, this may lead to overtreatment and has no effect on long-term hypoparathyroidism. Current recommendations on the management of post-thyroidectomy hypoparathyroidism is based on low-quality evidence. Existing guidelines do not often distinguish between surgical and non-surgical hypoparathyroidism, and transient and long-term disease.The aim of this systematic review was to summarise evidence on the use of calcium, vitamin D and recombinant parathyroid hormone in the management of post-thyroidectomy hypoparathyroidism. In addition, we aimed to highlight deficiencies in the current literature and stimulate further work in this field. OBJECTIVES The objective of this systematic review was to assess the effects of calcium, vitamin D and recombinant parathyroid hormone in managing post-thyroidectomy hypoparathyroidism. SEARCH METHODS We searched CENTRAL, MEDLINE, PubMed, Embase as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 17 December 2018 (except Embase, which was last searched on 21 December 2017). No language restrictions were applied. SELECTION CRITERIA We planned to include randomised control trials (RCTs) or controlled clinical trials (CCTs) examining the effects of calcium, vitamin D or recombinant parathyroid hormone in people with temporary and long-term post-thyroidectomy hypoparathyroidism. DATA COLLECTION AND ANALYSIS Two review authors independently screened titles, abstracts and full texts for relevance. MAIN RESULTS Database searches yielded a total of 1751 records. We retrieved potentially relevant full texts and excluded articles on the following basis: not a RCT or CCT; intervention, comparator or both did not match prespecified criteria; non-surgical causes of hypoparathyroidism, and studies on prevention. None of the articles was eligible for inclusion in the systematic review. AUTHORS' CONCLUSIONS This systematic review highlights a gap in the current literature and the lack of high-quality evidence in the management of post-thyroidectomy temporary and long-term hypoparathyroidism. Further research focusing on clinically relevant outcomes is needed to examine the effects of current treatments in the management of temporary and long-term post-thyroidectomy hypocalcaemia.