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Background: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life., Objectives: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo., Search Methods: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022., Selection Criteria: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D 3 ) or ergocalciferol (vitamin D 2 )., Data Collection and Analysis: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason., Main Results: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm 2 , 95% confidence interval (CI) -0.11 to 0.03; I 2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm 2 , 95% CI -0.06 to 0.06; I 2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I 2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I 2 = 72%; 2 studies, 541 participants; low-certainty evidence)., Authors' Conclusions: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer., Objectives: To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations., Search Methods: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews., Selection Criteria: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer., Data Collection and Analysis: Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach., Main Results: In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence)., Authors' Conclusions: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

Background: Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity., Objectives: To evaluate the efficacy and safety of dietary interventions on IBD outcomes., Search Methods: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines., Selection Criteria: We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded., Data Collection and Analysis: Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE., Main Results: The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events., Authors' Conclusions: The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.

Background: Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence., Objectives: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps., Search Strategy: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit , and Embase, to July 2007. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized., Selection Criteria: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study., Data Collection and Analysis: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model., Main Results: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined., Authors' Conclusions: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.

Background: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis., Objectives: To assess the effects of calcium on bone density and fractures in postmenopausal women., Search Strategy: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings., Selection Criteria: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion., Data Collection and Analysis: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio., Main Results: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72)., Authors' Conclusions: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Background: Decreased bone mineral density (BMD) occurs more commonly in patients with HIV than in the general population, making this group more susceptible to fragility fractures. However, bone loss is under-treated in patients with HIV., Objectives: To assess the effects of interventions aimed at increasing bone mineral density in HIV-infected adults., Search Strategy: We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, National Institutes of Health Clinical Trials Registry, and CenterWatch (search date July 2006)., Selection Criteria: Randomised trials comparing any pharmacological or non-pharmacological therapy with placebo, no treatment, or an alternative therapy, with the goal of increasing bone mineral density in adult (age 18 years or over) patients with HIV., Data Collection and Analysis: Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, conflicts were resolved with discussion and/or trial authors were contacted for further details., Main Results: Three completed randomised-controlled studies examined the role of alendronate in patients with HIV and osteopenia or osteoporosis. When all three studies were combined, much heterogeneity was seen (p<0.0001), most likely due to different populations and interventions. A sensitivity analysis showed that in two studies without heterogeneity (p=0.11), alendronate, calcium and vitamin D improved lumbar BMD after one year when compared with calcium and vitamin D (weighted mean difference +2.65 95% confidence interval (CI) 0.80, 4.51 percent). However the alendronate group did not have less fragility fractures, relative risk (RR) 1.28 (95% CI 0.20, 8.21), or osteoporosis, RR 0.50 (95% CI 0.24, 1.01). Adverse events were not significantly different between groups, RR 1.28 (95% 0.20, 8.21). One randomised-controlled study done in patients with AIDS wasting found that after three months, testosterone enanthane improved lumbar BMD compared to placebo by +3.70 (95% CI 0.48, 6.92) percent, but progressive resistance training did not improve lumbar BMD (+0.40 95% CI -2.81, 3.61 percent). No group in this study had any adverse effects., Authors' Conclusions: The very limited data reviewed showed that bisphosphonate therapy andin those with AIDS wasting syndrome, testosteronemay be safe and possibly effective methods to improve bone mineral density in HIV patients. The available studies are small, of short duration, and not powered to detect changes in WHO categories and fracture rates. Larger studies using bisphosphonates are currently underway. The role of colecalciferol, androgen replacement in women, and growth hormone are also under investigation.

Background: Metabolic studies suggest calcium may have a role in the regulation of blood pressure. Some epidemiological studies have reported that people with a higher intake of calcium tend to have lower blood pressure. Previous systematic reviews and meta-analyses have reached conflicting conclusions about whether oral calcium supplementation can reduce blood pressure., Objectives: To evaluate the effects of oral calcium supplementation as a treatment for primary hypertension in adults., Search Strategy: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review., Selection Criteria: Inclusion criteria were: 1) RCTs comparing oral calcium supplementation with placebo, no treatment, or usual care; 2) treatment and follow-up >/=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg; 4) SBP and DBP reported at end of follow-up. We excluded trials where: participants were pregnant; received antihypertensive medication which changed during the study; or calcium supplementation was combined with other interventions., Data Collection and Analysis: Two reviewers independently abstracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted., Main Results: We included 13 RCTs (n=485), with between eight and 15 weeks follow-up. The results of the individual trials were heterogeneous. Combining all trials, participants receiving calcium supplementation as compared to control had a statistically significant reduction in SBP (mean difference: -2.5 mmHg, 95% CI: -4.5 to -0.6, I(2 )= 42%), but not DBP (mean difference: -0.8 mmHg, 95% CI: -2.1 to 0.4, I(2) = 48%). Sub-group analyses indicated that heterogeneity between trials could not be explained by dose of calcium or baseline blood pressure. Heterogeneity was reduced when poor quality trials were excluded. The one trial reporting adequate concealment of allocation and the one trial reporting adequate blinding yielded results consistent with the primary meta-analysis., Authors' Conclusions: In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of calcium supplementation on blood pressure and cardiovascular outcomes.

Background: Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence., Objectives: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps., Search Strategy: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized., Selection Criteria: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study., Data Collection and Analysis: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model., Main Results: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined., Authors' Conclusions: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.

Background: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis., Objectives: To assess the effects of calcium on bone density and fractures in postmenopausal women., Search Strategy: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings., Selection Criteria: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion., Data Collection and Analysis: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio., Main Results: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72)., Reviewer's Conclusions: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Background: Several dietary factors have been considered to be involved in the increasing incidence of colorectal cancer in industrialised countries. Experimental and epidemiological evidence has been suggestive but not conclusive for a protective role for high dietary calcium intake. Intervention studies with colorectal cancer as an endpoint are difficult to perform owing to the large number of patients and the long follow-up required; studies using the appearance of colorectal adenomatous polyps as a surrogate endpoint are therefore considered in reviewing the existing evidence., Objectives: This systematic review aims to assess the effect of supplementary dietary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps., Search Strategy: We searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The reference lists of identified studies were inspected for further studies, and the review literature was scrutinized., Selection Criteria: Randomised controlled trials of the effects of dietary calcium on the development of colonic cancer and adenomatous polyps in humans are reviewed. Studies of healthy adults and studies of adults at higher risk of colon cancer due to family history, previous adenomatous polyps, or inflammatory bowel disease were considered; data from subjects with familial polyposis coli are excluded. The primary outcomes were the occurrence of colon cancer, and occurrence or recurrence of any new adenomas of the colon. Secondary outcomes were any adverse event that required discontinuation of calcium supplementation, and drop-outs before the end of the study., Data Collection and Analysis: Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. The outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). The data were combined with the fixed effects model., Main Results: Two studies with 1346 subjects met the inclusion criteria. Both trials were well designed, double - blind, placebo controlled trials, included participants with previous adenomas. The doses of supplementary elemental calcium used were 1200 mg daily for a mean duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials were combined., Reviewer's Conclusions: Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.

Background: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis., Objectives: To assess the effects of calcium on bone density and fractures in postmenopausal women., Search Strategy: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings., Selection Criteria: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion., Data Collection and Analysis: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio., Main Results: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72)., Reviewer's Conclusions: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.