Search

In December 2019, Corona Virus Disease 2019 (COVID-19) was first identified and designated as a pandemic in March 2020 due to rapid spread of the virus globally. At the beginning of the pandemic, only a few treatment options, mainly focused on supportive care and repurposing medications, were available. Due to its effects on immune system, vitamin D was a topic of interest during the pandemic, and researchers investigated its potential impact on COVID-19 outcomes. However, the results of studies about the impact of vitamin D on the disease are inconclusive. In the present narrative review, different roles of vitamin D regarding the COVID-19 have been discussed to show that vitamin D supplementation should be recommended carefully., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women., Methods: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI)., Results: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved., Conclusion: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40-79 years were followed up for a median of 20.36 years (20.32-20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women., (© 2020. The Author(s).)

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.)

Oral calcium salts are recommended for the treatment of chronic hypoparathyroidism (HypoPT), although dosimetry is variable between individual patients and clinicians. However, patient feedback on calcium salts can be negative, particularly due to gastrointestinal side effects and hypercalciuria-related complications. We begin with a clinical case of a HypoPT patient taking oral calcium salts following thyroid surgery, who requested support in reducing her dose of these with a view to stopping entirely. To evaluate her request, we first describe the usual treatment of HypoPT according to current guidance and then present data from (a) a case note review of a cohort of 24 HypoPT patients managed with a "no calcium" treatment regimen by single physician (b) a comprehensive online survey of HypoPT patients' treatment and experiences (n = 330). The case note review found that target range serum calcium levels were successfully achieved in all 24 patients since transitioning to a "no calcium" regimen, without any breakthrough hypocalcaemia-related symptoms, the development of new renal stones, the occurrence of calcium-related hospital admissions or the finding of significant hypercalciuria. The online survey identified 36% of HypoPT patients who continued to take activated vitamin D, but had discontinued calcium supplements. HypoPT patients not currently taking calcium reported a significantly lower prevalence of adverse effects and outcomes, both compared with their previous experiences whilst taking calcium and also compared with the 64% of patients who continued to take oral calcium. We conclude that, subject to methodological limitations, there are significant issues of tolerability arising from conventional calcium-based treatment regimens for patients with chronic HypoPT. For selected patients, it may be reasonable to facilitate a managed therapeutic transition to "no calcium" regimen, and we also propose that calcium-based regimes be prospectively evaluated against calcium-free (or calcium-low) alternatives., (© 2019 John Wiley & Sons Ltd.)

If all adults with osteoporosis in the European Union (EU) and United States (US) used calcium and vitamin D supplements, it could prevent more than 500,000 fractures/year in the EU and more than 300,000/year in the US and save approximately €5.7 billion and US $3.3 billion annually., Purpose: Evaluate the cost-effectiveness of calcium/vitamin D supplementation for preventing osteoporotic fractures., Methods: A cost-benefit analysis tool was used to estimate the net cost savings from reduced fracture-related hospital expenses if adults with osteoporosis in the EU and US used calcium/vitamin D supplements. A 14% relative risk reduction of fracture with calcium/vitamin D supplementation from a recent systematic review and meta-analysis of randomized, controlled trials was used as the basis for the benefit estimate. Other model inputs were informed by epidemiologic, clinical, and cost data (2016-2017) obtained via the medical literature or public databases. Analyses estimated the total number of avoided fractures and associated cost savings with supplement use. Net cost benefit was calculated by subtracting the supplements' market costs from those savings., Results: The > 30 million persons in the EU and nearly 11 million in US with osteoporosis experience about 3.9 million and 2.3 million fractures/year and have annual hospital costs exceeding €50 billion and $28 billion. If all persons with osteoporosis used calcium and vitamin D supplements, there would be an estimated 544,687 fewer fractures/year in the EU and 323,566 fewer in the US, saving over €6.9 billion and $3.9 billion; the net cost benefit would be €5,710,277,330 and $3,312,236,252, respectively., Conclusions: Calcium and vitamin D supplements are highly cost-effective, and expanded use could considerably reduce fractures and related costs. Although these analyses included individuals aged ≥ 50 years, the observed effects are likely driven by benefits observed in those aged ≥ 65 years.

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. The prevalence of both obesity and vitamin D deficiency has increased dramatically in Jordan in recent decades, especially among women. Few studies in Jordan and the surrounding area address this issue. In this study, we hypothesize that calcium and vitamin D have beneficial effects on weight reduction and metabolic profile in obese women. The objective of this study is to examine the effect of vitamin D 3 and calcium supplementation on anthropometric measurements and some blood metabolites. Forty-five obese female subjects with vitamin D deficiency were recruited by a dietitian and randomly assigned to the same weight loss diet in addition to the following treatments (4 groups): control (CON), no prescribed supplements; vitamin D 3 (Diet/D), given a high weekly dose of cholecalciferol (50 000 IU/subject/week); calcium (Diet/Ca), given 1200 mg/dL calcium/subject/day; vitamin D 3 plus Ca (Diet/Ca/D), given cholecalciferol (50 000 IU/subject/week) and calcium (1200 mg/dL calcium/subject/day). Results revealed that after 3 months of supplementation, the Diet/Ca/D group subjects experienced a significant reduction (P ≤ .05) in weight (10.49 kg), BMI (4.61 ± 2 kg/m 2 ), waist circumference (11.41 ± 8.9 cm), body fat percentage (2.43 ± 1.7%), FBG (25.81 ± 11.4 mg/dL), PTH (27.58 ± 8.9 pg/mL), cholesterol (0.56 ± 0.2 mmol/L), and triglycerides (0.53 ± 0.21 mmol/L) when compared to the Diet/Ca and the CON groups. Interestingly, however, the CON group showed a significant increase in serum PTH concentration (9.51 ± 3.8 pg/mL, P ≤ .05). Based on these results, a combined Ca and vitamin D 3 supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: osteoporosis is a metabolic bone disease that leads to increased bone fragility and increased risk of fracture., Objectives: the aim of the present research was to determine the effectiveness of a diary intake of three different dairy products (250 ml) enriched with vitamins and calcium on decreasing bone mass. METHOS: the present study is a comparative trial of three dairy products fortified with calcium and vitamin D, parallel, randomized, double-blind andsingle-center. Bone mass content (BMC), bone mass density (BMD), T-score and Z-score were measured in different locations, besides biochemical markers along 18 months in premenopausal women. Two hundred and ten volunteers from all the three groups were submitted to the same monitoring procedures, consisting on blood extraction, urine collection and energy X-ray absorptiometry (DEXA) done in the laboratory. The monitoring was carried on three times, first at month 0 (baseline), the second at month 9 (in the middle of the treatment) and, finally, at month 18 (the end of the treatment)., Results: the majority of anatomical locations showed both BMC and BMD decrease ranging between 0.5% and 1.5%. The T-score and the Z-scoreincreased in lumbar spine after the treatment with the dairy products. Moreover, the most noteworthy change on the biomarkers of bone resorption was showed by plasmatic tartrate-resistant acid phosphatase (TRAP), with and increase between 20.7% and 29.5% after the intake of the different products., Conclusions: therefore, the intake of the three dairy products improves the bone mass in lumbar spine, leading to important changes in the concentration of biomarkers of bone resorption. Especially, tartrate-resistant acid phosphatase seems to be strongly influenced by the intake of every dairy product. However, no significant differences were found between the different dairy products used in the present study. Therefore, the intake of dairy product seems to be more determinant than micronutrients supplementation.

Introduction: In this paper we investigated whether cholecalciferol supplementation, prescribed to treat vitamin D deficiency in patients with nephrolithiasis, increased the risk of stone recurrence., Methods: Calcium excretion and urine supersaturation with calcium oxalate (βCaOx) and brushite (βbsh) were evaluated in 33 kidney stone formers (aged 56±17; 12 males), both before and after therapy with cholecalciferol, prescribed as oral bolus of 100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000-10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a dietary regimen which included a daily calcium intake of about 800-1000 mg., Results: Urinary nitrogen, sodium and ash-acid excretion did not significantly change during the study. After cholecalciferol supplementation, the main results were as follows: both serum calcium and phosphate did not vary significantly; 25(OH)VitD₃ increased from 11,8±5,5 to 40,2±12,2 ng/mL (p<0,01); 1,25(OH) ₂ VitD₃ increased from 41,6±17,6 to 54,0±16,0 pg/mL (p<0,01); PTH decreased from 75,0±27,2 to 56,7±21,1 pg/mL (p<0,01); daily urinary calcium increased from 2,7±1,5 to 3,6±1,6 mg/Kg b.w. (p<0,01), whereas fasting urinary calcium did not change significantly. After therapy, βbsh increased from 0,9±0,7 to 1,3±1,3 (p=0,02) and βCaOx did not vary significantly. Before cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric, whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation (pX²=0,03)., Conclusions: Cholecalciferol supplementation for vitamin D deficiency may increase both urinary calcium and urine supersaturation in stone formers. If vitamin D supplements are needed in these patients, a careful monitoring of urine metabolic profile is warranted, in order to customize the metaphylaxis accordingly (hydration, potassium citrate, thiazides)., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Adverse effects of low vitamin D status and calcium intakes in pregnancy may be mediated through functional effects on the calcium metabolic system. Little explored in pregnancy, we aimed to examine the relative importance of serum 25-hydroxyvitamin D (25(OH)D) and calcium intake on parathyroid hormone (PTH) concentrations in healthy white-skinned pregnant women. This cross-sectional analysis included 142 participants (14 ± 2 weeks' gestation) at baseline of a vitamin D intervention trial at 51.9 °N. Serum 25(OH)D, PTH, and albumin-corrected calcium were quantified biochemically. Total vitamin D and calcium intakes (diet and supplements) were estimated using a validated food frequency questionnaire. The mean ± SD vitamin D intake was 10.7 ± 5.2 μg/day. With a mean ± SD serum 25(OH)D of 54.9 ± 22.6 nmol/L, 44% of women were <50 nmol/L and 13% <30 nmol/L. Calcium intakes (mean ± SD) were 1182 ± 488 mg/day and 23% of participants consumed <800 mg/day. The mean ± SD serum albumin-adjusted calcium was 2.2 ± 0.1 mmol/L and geometric mean (95% CI) PTH was 9.2 (8.4, 10.2) pg/mL. PTH was inversely correlated with serum 25(OH)D ( r = -0.311, p < 0.001), but not with calcium intake or serum calcium ( r = -0.087 and 0.057, respectively, both p > 0.05). Analysis of variance showed that while serum 25(OH)D (dichotomised at 50 nmol/L) had a significant effect on PTH ( p = 0.025), calcium intake (<800, 800⁻1000, ≥1000 mg/day) had no effect ( p = 0.822). There was no 25(OH)D-calcium intake interaction effect on PTH ( p = 0.941). In this group of white-skinned women with largely sufficient calcium intakes, serum 25(OH)D was important for maintaining normal PTH concentration.

Objectives: To determine the incidence of hypovitaminosis D and to evaluate a supplementation intervention. We hypothesized that patients would exhibit high adherence with a free sample, and levels would become sufficient., Design: Prospective observational study., Setting: Level 1 trauma center., Patients: One hundred forty-four consecutive, skeletally mature patients treated for acute fractures., Intervention: All were provided 600 mg calcium and 800 IU vitamin D3 capsules twice daily., Main Outcome Measurements: Serum 25(OH) D levels were obtained on presentation and after supplementation. Patient surveys determined adherence, vitamin D intake, and sun exposure., Results: Ninety-one men and 53 women, mean age 45 years, mean body mass index 28.1, were studied. Mean baseline 25(OH) D level was 20.2 ng/mL, including 9 patients taking vitamin D supplements before injury. All others (mean baseline 16.9 ng/mL) were prescribed calcium and vitamin D and were offered free supplements when discharged. Seventy-seven patients completed surveys, and mean 25(OH) D level was 36.7 ng/mL after a mean of 7.0 weeks of supplementation (P < 0.0001). Seventy-nine percent reported adherence to supplement recommendations. All adherent patients achieved normal levels. Sixteen patients were nonadherent, with 10 who forgot to take the supplement, 4 choosing not to use it, 1 choosing to sell the sample, and 1 losing the sample., Conclusion: Hypovitaminosis D was present in 97% of orthopaedic trauma patients who were not already taking supplements. The intervention was effective in reducing hypovitaminosis D within several weeks, with all supplemented patients achieving normal levels. Seventy-nine percent of patients adhered to recommendations. Further study to determine the long-term cost-effectiveness of this strategy seems warranted., Level of Evidence: Therapeutic, Level II. See Instructions for Authors for a complete description of levels of evidence.

The World Health Organization (WHO) recommends calcium supplementation for prevention of pre-eclampsia, but factors affecting adoption and acceptability of the recommendations among pregnant women have not been examined. We explored adoption of the WHO guidelines in Kenya, using the trials of improved practices. We recruited 38 pregnant women and assigned participants to three regimens representing potential trade-offs among daily dose, bioavailability, and acceptability. Participants were provided with supplements, requested to select preferred product type, counselled on how to take them, and interviewed 4 times over 6 weeks to assess their experiences. We tracked bottle opening with electronic monitors, as proxy for supplement consumption. We analysed interview transcripts thematically. All participants were willing to try the supplements. Average daily consumption ranged from 77 to 1,577 mg/d. Most participants (74%) chose the chewable product. Participants preferred its "sweet taste" and liked the ability to consume it without water. Women in the 2-dose regimen were least likely to switch; however, women assigned to the 3-dose regimen, or who switched to the 3-dose regimen, consumed the most calcium per day. Difficulties with the 4-dose regimen included afternoon doses when women were likely to forget and having to wait hours after supper for last dose. Use of an illustrated calendar, keeping supplements in conspicuous locations and requesting support from relatives were strategies that supported adherence. Pregnant women are likely to adopt Ca supplementation, with appropriate programmatic adaptations. Careful attention to product attributes, regimen complexity, and strategies for reassuring and reminding women are needed to adapt the WHO guidelines., (© 2017 John Wiley & Sons Ltd.)

Purpose: Some research findings suggest that calcium plus vitamin D (VitD) might have a preventive effect on nonalcoholic fatty liver disease development. Moreover, contradictory evidence also exists regarding calcium and VitD deficient diets. This study aimed to evaluate the effect of four different dietary calcium and VitD 3 (cholecalciferol) levels on the development of high-fat, high-fructose (HFHFr) diet-induced nonalcoholic fatty liver disease and AMP-activated protein kinase (AMPK) phosphorylation., Methods: Thirty male Wistar rats were fed with normal or HFHFr diet containing low calcium (0.2%) and VitD 3 (250 IU/kg) (LCD), normal calcium (0.5%) and VtD 3 (1000 IU/kg) (CN), high calcium (1.2%) and VitD 3 (4000 IU/kg) (HCD) or very high amount of calcium (2.4%) and VitD 3 (10,000 IU/kg) (VHCD). After 60 days, anthropometric, metabolic and hepatic parameters were evaluated. The effect of the experimental diets on liver AMPK phosphorylation was also investigated., Results: Rats fed on high calcium plus VitD 3 diets, especially VHCD, demonstrated lower adiposity, serum liver enzymes, hepatic lipid accumulation and steatosis. The LCD diet also decreased hepatic lipid content and fatty changes. No evidence indicating the involvement of AMPK in the observed associations was found (P value = 0.51)., Conclusions: The results showed high calcium plus VitD 3 intakes considerably prevent biochemical and hepatic changes induced by HFHFr diet, probably via an insulin and AMPK-independent pathway. A low intake of these two nutrients was also linked with a significant decrease in HFHFr diet-induced hepatic steatosis.

Introduction: Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved., Aims: To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines., Materials and Methods: Literature review and consensus of expert opinion., Results and Conclusion: The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Adequate calcium intake during pregnancy is important in the prevention of pre-eclampsia. A substantial proportion of pregnant women do not meet the recommended daily calcium intake, even in developed countries. Nonetheless, calcium supplementation is not routinely advised to pregnant women in most countries. We aimed to predict the impact of advising pregnant women to use calcium supplements (1,000 mg/day) on the number of cases of pre-eclampsia prevented and related health care costs. By use of a decision-analytic model, we assessed the expected impact of advising calcium supplementation to either (1) all pregnant women, (2) women at high risk of developing pre-eclampsia, or (3) women with a low dietary calcium intake compared with current care. Calculations were performed for a hypothetical cohort of 100,000 pregnant women living in a high-income country, although input parameters of the model can be adjusted so as to fit other settings. The incidence of pre-eclampsia could be reduced by 25%, 8%, or 13% when advising calcium supplementation to all pregnant women, women at high risk of pre-eclampsia, or women with a low dietary calcium intake, respectively. Expected net financial benefits of the three scenarios were of €4,621,465, €2,059,165, or €2,822,115 per 100,000 pregnant women, respectively. Advising pregnant women to use calcium supplements can be expected to cause substantial reductions in the incidence of pre-eclampsia as well as related health care costs. It appears most efficient to advise calcium supplementation to all pregnant women, not subgroups only., (© 2017 John Wiley & Sons Ltd.)

Background: Evidence supports the role of lifestyle interventions as a primary intervention strategy among individuals with dyslipidemia. The role of micronutrients, and calcium in particular, on cholesterol metabolism is not clear and warrants further investigation., Objective: The aim of this study is to conduct a meta-analysis of controlled clinical trials that have examined the effects of calcium supplements on blood lipids among adults., Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for calcium supplements clinical trials. Other trials were selected from searching bibliography of reviews, meta-analysis, and included trials. Clinical trials with random allocation to calcium supplementation or calcium plus vitamin D supplementation, or control were selected. Data collected included study design, participant characteristics, information of the intervention, and outcomes. Data synthesis was conducted using random effect models., Results: A total of 22 trials, representing 4071 participants, met the eligibility criteria. Compared with control group, calcium supplements significantly reduced low-density lipoprotein cholesterol level by -0.12 mmol/L (95% confidence interval, -0.22 to -0.02) and increased high-density lipoprotein cholesterol level by 0.05 mmol/L (95% confidence interval, 0.00 to 0.10). Subgroup analyses revealed that the associations were consistent across study duration and vitamin D cosupplementation status., Conclusions: Calcium supplementation has beneficial effect on blood lipids. Such supplements may be useful as a nonpharmaceutical strategy in cholesterol control.

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)]., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vitamin D-dependent rickets type 2A (VDDR2A) is a rare inherited disorder with decreased tissue responsiveness to 1,25-dihydroxyvitamin D [1,25(OH) 2 D], caused by loss of function mutations in the vitamin D receptor (VDR) gene. Approximately 50 types of mutations have been identified so far that change amino acids in either the N-terminal DNA binding domain (DBD) or the C-terminal ligand binding domain (LBD) of the VDR protein. The degree of responsiveness to 1,25(OH) 2 D varies between patients with VDDR2A, which may depend on their residual VDR function. In this report, we describe a female patient with VDDR2A caused by an early stop codon (R30X) in the VDR gene that resulted in a severely truncated VDR protein. She developed alopecia and bowed legs within a year after birth and was diagnosed with rickets at the age of 2. She had been treated with active vitamin D and oral calcium supplementation until 22 years of age, when she developed secondary hyperparathyroidism and high bone turnover. The genetic diagnosis of VDDR2A promoted the discontinuation of active vitamin D treatment in favor of monotherapy with oral calcium supplementation. We observed amelioration of the secondary hyperparathyroidism and normalization of bone metabolic parameters within 6 years.

Osteoporosis (low bone strength) and sarcopenia (low muscle mass, strength and/or impaired function) often co-exist (hence the term 'sarco-osteoporosis') and have similar health consequences with regard to disability, falls, frailty and fractures. Exercise and adequate nutrition, particularly with regard to vitamin D, calcium and protein, are key lifestyle approaches that can simultaneously optimize bone, muscle and functional outcomes in older people, if they are individually tailored and appropriately prescribed in terms of the type and dose. Not all forms of exercise are equally effective for optimizing musculoskeletal health. Regular walking alone has little or no effect on bone or muscle. Traditional progressive resistance training (PRT) is effective for improving muscle mass, size and strength, but it has mixed effects on muscle function and falls which may be due to the common prescription of slow and controlled movement patterns. At present, targeted multi-modal programs incorporating traditional and high-velocity PRT, weight-bearing impact exercises and challenging balance/mobility activities appear to be most effective for optimizing musculoskeletal health and function. Reducing and breaking up sitting time may also help attenuate muscle loss. There is also evidence to support an interaction between exercise and various nutritional factors, particularly protein and some multi-nutrient supplements, on muscle and bone health in the elderly. This review summary provides an overview of the latest evidence with regard to the optimal type and dose of exercise and the role of various nutritional factors for preventing bone and muscle loss and improving functional capacity in older people.

Background: Fracture is a complex trait, affected by both genetic and environmental factors. A meta-analysis of genome-wide association studies (GWASs) identified multiple bone mineral density (BMD) and fracture-associated loci. Objective: We conducted a study to evaluate whether fracture genetic risk score (Fx-GRS) and bone mineral density genetic risk score (BMD-GRS) modify the association between the intake of calcium with vitamin D (CaD) and fracture risk. Design: Data from 5823 white postmenopausal women from the Women's Health Initiative CaD randomized trial were included. Participants received 1000 mg elemental Ca with 400 IU vitamin D 3 /d or placebo (median follow-up: 6.5 y). Total fracture was defined as first fracture of any type. We computed the Fx-GRS with 16 fracture- and BMD-associated variants, and the BMD-GRS with 50 BMD-associated variants. We used Cox regression and a case-only approach to test for multiplicative interaction. Additive interaction was assessed with the relative excess risk due to interaction (RERI). We analyzed genetic risk score as a continuous variable and a categorical variable based on quartile (quartile 1, quartiles 2-3, and quartile 4). Results: We observed no interaction between the Fx-GRS and CaD on fracture risk; however, we observed a significant multiplicative interaction between the BMD-GRS and CaD assignment ( P -interaction = 0.01). In addition, there was a significant negative additive interaction between placebo assignment and higher BMD-GRS: quartiles 2-3, P RERI = 0.03; quartile 4, P RERI = 0.03. In a stratified analysis, the protective effect of CaD on fracture risk was observed in women in the lowest BMD-GRS quartile (HR: 0.60, 95% CI: 0.44, 0.81) but not in women with a higher BMD-GRS. Conclusions: We observed significant effects of CaD intake on fracture risk only in women with the lowest genetic predisposition to low BMD. Future large-scale studies with functional characterization of GWAS findings are warranted to assess the utility of genetic risk score in analysis of risks and benefits of CaD for bone., (© 2017 American Society for Nutrition.)

Purpose: DNA methylation is one of the most extensively studied mechanisms within epigenetics, and it is suggested that diet-induced changes in methylation status could be involved in energy metabolism regulation. Conjugated linoleic acid (CLA) and calcium supplementation counteract body weight gain, particularly under a high-fat (HF) diet, in adult mice. The aim was to determine whether the modulation of DNA methylation pattern in target genes and tissues could be an underlying mechanism of action., Methods: Mice (C57BL/6J) were divided into five groups according to diet and treatment: normal fat as the control group (12 % kJ content as fat), HF group (43 % kJ content as fat), HF + CLA (6 mg CLA/day), HF + calcium (12 g/kg of calcium) and HF with both compounds. Gene expression and methylation degree of CpG sites in promoter sequences of genes involved in fatty acid metabolism, including adiponectin (Adipoq), stearoyl-CoA desaturase (Scd1) and fatty acid synthase (Fasn), were determined by bisulphite sequencing in liver and epididymal white adipose tissue., Results: Results showed that the methylation profile of promoters was significantly altered by dietary supplementation in a gene- and tissue-specific manner, whereas only slight changes were observed in the HF group. Furthermore, changes in specific CpG sites were also associated with an overall healthier metabolic profile, in particular for calcium-receiving groups., Conclusions: Both CLA and calcium were able to modify the methylation pattern of genes involved in energy balance in adulthood, which opens a novel area for increasing efficiency in body weight management strategies.

Background: Muscular weakness and severe vitamin D deficiency is prevalent in Somali (veiled) pregnant women, Sweden. The study aims here were to explore adherence to prescribed supplemental vitamin D in new mothers with vitamin D deficiency and its effects on grip strength and upper leg performance in Somali (target group TG) and Swedish women (reference group RG) from spring through winter., Methods: A before- and after study was designed. A cross-sectional sample of women in antenatal care with serum 25-OHD ≤50 nmol/L were prescribed one or two tablets daily (800 or 1600 IU vitamin D3 with calcium) for 10 months. Reminders were made by Somali nurses (TG) or Swedish doctors (RG). Baseline and 10 month measurements of plasma nmol/L 25-OHD, maximal grip strength held for 10 s (Newton, N) and ability to squat (yes;no) were done. Total tablet intake (n) was calculated. Outcome variables were changes from baseline in grip strength and ability to squat. Predicting variables for change in grip strength and ability to squat were calculated using linear and binary regression in final models. Undetectable 25-OHD values (<10 nmol/L) were replaced with '9' in statistic calculations., Results: Seventy-one women (46 TG, 1/3 with undetectable baseline 25-OHD; 25 RG) participated. At the 10-month follow up, 17% TG and 8% RG women reported having refrained from supplement. Mean 25-OHD increased 16 to 49 nmol/L (TG) and 39 nmol/L to 67 nmol/L (RG), (both p < 0.001). Grip strength had improved from 153 to 188 N (TG) (p < 0.001) and from 257 to 297 N (RG) (p = 0.003) and inability to squat had decreased in TG (35 to 9, p < 0.001). Intake of number of tablets predicted increased grip strength (B 0.067, 95%CI 0.008-0.127, p = 0.027). One tablet daily (>300 in total) predicted improved ability to squat (OR 16; 95% CI 1.8-144.6)., Conclusions: Adherence to supplemental vitamin D and calcium should be encouraged as an even moderate intake was associated to improved grip strength and upper leg performance, which was particularly useful for the women with severe 25-OHD deficiency and poor physical performance at baseline., Trial Registration: ClinicalTrials.gov Identifier: NCT02922803 . Date of registration: September 28, 2016.

Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

Background: Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC)., Methods and Results: We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79-1.14), 1.02 (0.85-1.23), 0.86 (0.69-1.05), and 0.73 (0.57-0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07-1.39]). No relation was found between baseline calcium intake and 10-year changes in log-transformed CAC among those participants with baseline CAC >0., Conclusions: High total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Calcium supplementation during pregnancy has been shown to reduce the incidence of pre-eclampsia/eclampsia among women with low calcium intake. Universal free calcium supplementation through government antenatal care (ANC) services was piloted in the Dailekh district of Nepal. Coverage, compliance, acceptability and feasibility of the intervention were evaluated., Methods: Antenatal care providers were trained to distribute and counsel pregnant women about calcium use, and female community health volunteers (FCHVs) were trained to reinforce calcium-related messages. A post-intervention cluster household survey was conducted among women who had given birth in the last six months. Secondary data analysis was performed using monitoring data from health facilities and FCHVs., Results: One Thousand Two hundred-forty postpartum women were interviewed. Most (94.6 %) had attended at least one ANC visit; the median gestational age at first ANC visit was 4 months. All who attended ANC were counseled about calcium and received calcium tablets to take daily until delivery.79.5 % of the women reported consuming the entire quantity of calcium they received. The full course of calcium (300 tablets for 150 days) was provided to 82.3 % of the women. Consumption of the full course of calcium was reported by 67.3 % of all calcium recipients. Significant predictors of completing a full course were gestational age at first ANC visit and number of ANC visits during their most recent pregnancy (p < 0.01). Nearly all (99.2 %) reported taking the calcium as instructed with respect to dose, timing and frequency. Among women who received both calcium and iron (n = 1,157), 98.0 % reported taking them at different times of the day, as instructed. Over 97 % reported willingness to recommend calcium to others, and said they would like to use it during a subsequent pregnancy. There were no stock-outs of calcium., Conclusions: Calcium distribution through ANC was feasible and effective, achieving 94.6 % calcium coverage of pregnant women in the district. Most women (over 80 %) attended ANC early enough in pregnancy to receive the full course of calcium supplements and benefit from the intervention. High coverage, compliance, acceptability among pregnant women and feasibility were reported, suggesting that this intervention can be scaled up in other areas of Nepal.

Background: The present study was designed to examine the effects of vitamin D plus calcium administration on metabolic profiles and pregnancy outcomes among women at risk for pre-eclampsia., Methods: In a prospective, double-blind, placebo-controlled trial, 60 women at risk for pre-eclampsia were randomised to take either 50 000 IU vitamin D3 every 2 weeks plus 1000 mg day(-1) calcium supplements (as calcium carbonate) (n = 30) or to receive placebos at the same times (n = 30) from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline and 12 weeks after intervention to determine related variables. Newborn anthropometric measurements were determined., Results: Taking combined cholecalciferol and calcium supplements, compared to placebo, led to significant reductions in fasting plasma glucose (FPG) [mean (SD)] [-5.7 (5.5) versus -0.6 (12.6) mg dL(-1) , P = 0.04], serum insulin concentrations [-2.8 (6.0) versus +7.7 (9.8) μIU mL(-1) , P < 0.001], homeostasis model of assessment-insulin resistance [-0.8 (1.3) versus +1.6 (2.2), P < 0.001], homeostatic model assessment-beta cell function [-8.2 (25.8) versus +32.6 (41.3, P < 0.001] and a significant rise in quantitative insulin sensitivity check index score [+0.02 (0.02) versus -0.02 (0.02, P < 0.001]. Additionally, pregnant women who received cholecalciferol plus calcium supplements had increased serum high-density lipoprotein (HDL)-cholesterol [+4.6 (8.3) versus -2.9 (7.7) mg dL(-1) , P = 0.001] and plasma total glutathione (GSH) concentrations [+23.4 (124.0) versus -94.8 (130.2) μm, P = 0.001] compared to placebo. However, after adjustment for the baseline levels, maternal age and baseline body mass index, the effects on FPG levels (P = 0.13) and systolic blood pressure (P = 0.13) disappeared., Conclusions: Vitamin D plus calcium administration for 12 weeks had beneficial effects on glycaemic status, HDL-cholesterol, GSH and blood pressure among women at risk for pre-eclampsia., (© 2015 The British Dietetic Association Ltd.)

Introducción: según la Organización Mundial de la Salud, la obesidad se puede definir como una acumulación anormal o excesiva de grasa que puede ser yatrogénica para la salud.Objetivo: resumir las revisiones sistemáticas Cochrane y no Cochrane que evalúen el efecto de la suplementación de calcio para la disminución del Índice de masa corporal en personas obesas.Materiales y métodos: se realizó una búsqueda en la base de datos Medline (1980 - septiembre de 2015), Metabuscador TripDatabase y Epistemonikos (hasta septiembre de 2015), Cochrane BVS (hasta septiembre de 2015); se buscó de forma manual en revistas relacionadas con el tema de interés; se buscaron actas de congresos y se realizaron seguimientos de referencias relevantes y se contactó con expertos en el área.Resultados: la búsqueda preliminar arrojó un total de 7.163 artículos potencialmente elegibles. Según los criterios de elegibilidad incluimos dos revisiones sistemáticas de estudios clínicos aleatorizados.Conclusión: el suplemento de calcio, al parecer, no incidiría en la disminución del índice de masa corporal, DM 0,12 (-0,62, 0,86); p = 0,75, presentando "muy baja evidencia" según GRADE, esto quiere decir que "presenta una gran incertidumbre sobre la estimación del efecto".

The WHO issued a strong recommendation that pregnant women be provided calcium supplements to prevent preeclampsia. This is the first recommended nutritional intervention to prevent this condition, a leading cause of maternal mortality globally. As health systems seek to implement this new intervention, a number of issues require further clarification and guidance, including dosage regimen, supplement formulation, and alignment with other antenatal nutritional interventions. We summarize key evidence on the above points and offer our views on good practices. Most developing countries have low calcium intake, so where habitual calcium intake is unknown, calcium supplements are likely beneficial. In our view, policymakers and program planners should consider adopting doses between 1.0 and 1.5 g elemental calcium/d, depending on the local average and variation in dietary calcium intake, logistical feasibility, and acceptability in the target population. Prudent practice would entail daily administration as calcium carbonate administered in divided doses of not >500 mg elemental calcium per dose. For ease of prescribing and adherence, calcium [as with iron and folic acid (IFA)] should be administered routinely to pregnant women from the earliest contact in pregnancy until delivery. Calcium's acute inhibitory effect on iron absorption translates to minimal effects in clinical studies. Therefore, to simplify the regimen and facilitate adherence, providers should not counsel that calcium and IFA pills must be taken separately. Although further research will shed more light on clinical and programmatic issues, policies can be implemented with ongoing revision as we continue to learn what works to improve maternal and newborn health., (© 2016 American Society for Nutrition.)

Recent literature suggests that Ca supplements have adverse effects on cardiovascular health. The effects of a Ca-rich supplement administered alone or in combination with short-chain fructo-oligosaccharides (scFOS) on serum lipids in postmenopausal women were examined using secondary data from a 24-month double-blind randomised controlled study. A total of 300 postmenopausal women were randomly assigned to daily supplements of 800 mg of Ca (2·4 g Aquamin) (Ca), 800 mg of Ca with 3 g of scFOS (CaFOS) or control (maltodextrin) (MD). A full lipid profile, body composition, blood pressure and a range of cytokines were measured at baseline and after 24 months. Intention-to-treat ANCOVA assessed treatment effects between the groups. A significant time-by-treatment effect was observed for LDL and total cholesterol for the Ca and CaFOS groups, with both groups having lower LDL and total cholesterol concentrations compared with MD after 24 months. The control group had mean (5·2 mmol/l) total cholesterol concentrations above the normal range (≤ 5 mmol/l) at 24 months, whereas values remained within the normal range in the treatment groups. There was no significant treatment effect on HDL-cholesterol, TAG, body composition, blood pressure or cytokine concentrations at 24 months, with the exception of IL-4, where there was a significant increase in the CaFOS group compared with the placebo. This study demonstrates a lipid-lowering effect of both the Ca-rich supplement alone and the supplement with scFOS. At the 4-year follow-up, there was no significant difference between the groups for reported diagnosed cardiovascular conditions.

Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

The aim of this study is to evaluate body composition and the bone mineral density in female adolescents with juvenile systemic lupus erythematosus. Body composition (BC) and bone mineral density (BMD) were evaluated in an observational cohort study with 35 postmenarcheal adolescent females. The variables studied were as follows: current and cumulative corticosteroid dose, intake of supplements containing calcium and vitamin D, 24-h proteinuria, body mass index (BMI), and height for age (Z-score). BC was assessed using dual-energy X-ray absorptiometry (DXA) at two time points (median interval of 1.2 years). The fat mass index (FMI = fat mass in kilograms divided by the height in meters squared) and lean mass index (LMI = lean mass in kilograms divided by the height in meters squared) were calculated based on the DXA results. BMD was classified according to the International Society of Clinical Densitometry (low BMD for chronological age < -2.0 standard deviations). .The mean age of the subjects was 15.4 ± 1.8 years. Of patients, 54.3 % were normal weight, 22.8 % were overweight, 22.8 % were obese, and 8.6 % had short stature. Low BMD for chronological age was observed in 42.8 % of patients, and 60 % were not taking vitamin D. There was no significant difference between the two time points with respect to FMI, LMI, or body mass index Z-score (ZBMI); however, BMD has decreased significantly (p = 0.011). There was an association between not taking a vitamin D supplement and decreased BMD (p = 0.027). Almost half of the patients had altered nutritional status. The BMD decrease in adolescents with juvenile systemic lupus erythematosus (JSLE) was associated with the lack of vitamin D supplementation, highlighting the importance of well-defined vitamin D supplementation protocols.

Background/objectives: Although previous studies reported that calcium supplementation can effectively improve bone mineral density in postmenopausal women, some studies showed the reverse conclusion. One of the reasons was that most of the studies did not take into full consideration the information of noncompliers, which seriously influenced the precision of conclusion. The aim of this paper was to investigate the effect of calcium supplementation on bone mineral density with correcting impact of noncompliance using the complier average causal effect (CACE)., Subjects/methods: A randomized controlled trial was designed to investigate the effect of high-calcium milk powder on bone mineral density. One hundred and forty-one postmenopausal women were randomly assigned to either a control group (n=72) or a milk powder supplementation group (n=69). The participants in the intervention group took 50 g of high-calcium milk powder containing 450 mg of elemental calcium and 400 IU vitamin D every morning and evening, respectively. The effects of the intervention on the primary outcome, bone mineral density, were assessed using the CACE model and intention-to-treat (ITT) and per-protocol (PP) analyses., Results: Using the CACE model, the calcium supplementation was found to significantly reduce the bone loss at the lumbar spine compared with the control group at 24 months when adjusting the covariates (effect size 1.170, 95% confidence interval (CI) 0.376~1.964, P=0.0040). At the hip site, there was no significant difference between the calcium group and the control group. Compared with the control group, no significant weight gain was found in the calcium group over 24 months. However, the calcium group had less height loss at 24 months (effect size 1.040, 95% CI 0.012~2.066, P=0.0470) than the control group. High-density lipoprotein was significantly increased in the calcium group at 12 months (effect size 0.120, 95% CI 0.009~0.232, P=0.0340). Serum total cholesterol, triglyceride and low-density lipoprotein were not affected over 24 months. The estimates of complier average causal effect of latent ignorability model with missing data assumption of latent ignorability were consistent with the CACE estimates., Conclusion: Consumption of high-calcium milk powder is effective in reducing the bone loss at the lumbar spine among healthy postmenopausal women. Supplementing with high-calcium milk powder had additional benefits of reducing height loss.

Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: n. The study was aimed at determining, on an animal model, effects of supplementing a diet, modified by substituting whole wheat and corn grains with white flour and sucrose, with calcium, magnesium, zinc, and chromium on metabolism of the minerals and their distribution in the body., Methods: The study involved 4 groups of Wistar rat females (n = 11) fed: a standard feed (group I) containing, i.a., whole wheat and corn grains; modified feed (84% and 50% of whole wheat and corn grains, respectively, in the standard feed substituted with Type 500 wheat flour and sucrose, respectively) (group II); modified feed with complementary supplementation (elimination of Ca, Mg, Zn, and Cr deficiencies resulting from diet modification) (group III); and modified feed with excess supplementation (the same minerals applied in excess, i.e., amounts from 0.5 to 3 times higher than the deficiencies produced by diet modification) (group IV). The replacement of whole grains with white flour and sucrose, as well as the mineral  supplementation could, to some extent, imitate the contemporary eating habits and supplementation applied in food technology. The excess supplementation is, on the other hand, typical of current behaviours of various social groups., Results: Both types of supplementation resulted in a significant increase in the perivisceral adipose tissue content, but did not affect the fat tissue content in muscles. The supplementation applied did not change the content of calcium, magnesium, and zinc in muscles, nor did it significantly change calcium and magnesium excretion with urine. However, changes in the ALP activity and calcitonin concentration did not suggest the deposition of the minerals in bones., Conclusions: Analysis of the results allowed to conclude that: 1) except for chromium, contents of the selected minerals in the tissues examined and urea, as well as concentrations of calcitonin and alkaline phosphatase (ALP) activities did not point to any significant effect of the supplementation applied on the body contents of those minerals; 2) effects observed as the accumulation of perivisceral, epicardial and intramuscular adipose tissue, as well as increased body weight increments could have been related to disturbed proportions of the minerals supplemented, their synergy and antagonism and, consequently, a potential generation of secondary deficiencies and excesses which could significantly affect individual metabolic pathways; 3) the intensity of changes observed was generally higher in the females receiving complementary supplementation, although their uptake of minerals studied was similar to that shown by the females kept on the standard diet.

Calcium and vitamin D modify the molecular phenotypic profiles of colon crypts in the normal colorectal mucosa of colorectal adenoma patients, but their effects on crypt morphology (length, perimeter, and area) are unknown. We analyzed data from a previously conducted pilot, randomized, double-blind, placebo-controlled 2 × 2 factorial chemoprevention clinical trial of supplemental calcium 2000 mg/d and vitamin D3 800 IU/d, alone and in combination, versus placebo over 6 mo. Colorectal crypt length, perimeter, and area in the normal-appearing rectal mucosa were quantified by image analysis. The mean crypt length increased by 1% (P=0.92) in the calcium group, and decreased by 2% (P=0.69) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. The mean crypt perimeter decreased by 2% (P=0.70) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group, but did not change appreciably in the calcium group. The mean crypt area decreased by 2% (P=0.74), 5% (P=0.41) and 7% (P=0.30) in the calcium, vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. Calcium and/or vitamin D3 supplementation do not appear to appreciably change crypt morphology in the normal colorectal mucosa of sporadic adenoma patients. These results, taken together with previous findings, support the use of molecular phenotypic over morphologic pre-neoplastic biomarkers of risk for colorectal neoplasms., (© 2013 Wiley Periodicals, Inc.)

Long-term management of patients with differentiated thyroid cancer (DTC) commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal health. Experience with female patients treated for DTC at a young age and who were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very limited to date. This cross-sectional study set out to investigate effects of Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and followed-up for an average of 10 years. BMD was found to be significantly higher in patients receiving Calcium-D3 medication than in patients not taking supplements. The level of ionized calcium was the strongest factor determining lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy ending in childbirth and HDL-cholesterol were associated with a weak adverse effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect BMD in women treated for DTC at young age, at least after 10 years of follow-up.

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta-analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta-analyses. We, therefore, undertook a meta-analysis of randomized controlled trials with placebo or no-treatment control groups to determine if these supplements increase all-cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random-effects meta-analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96-1.09; p = 0.51). Seventeen trials contributed all-cause mortality data with pooled RR of 0.96 (95% CI, 0.91-1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I(2)  = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92-1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95-1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73-1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all-cause mortality risk in elderly women., (© 2014 American Society for Bone and Mineral Research.)

Background: Up to 75% of the risk of type 2 diabetes is attributable to obesity. Therefore, finding a way to control obesity can be useful for management of diabetes., Objective: This study was performed to assess the effects of vitamin D3 and calcium supplementation on anthropometric measurements and blood pressure in vitamin D insufficient people with type 2 diabetes., Methods: One hundred eighteen patients with diabetes were enrolled in this randomized placebo-controlled clinical trial. All subjects were randomly assigned into 4 groups receiving (1) 50,000 IU/wk vitamin D3 plus (equal to 7143 IU/d) calcium placebo; (2) 1000 mg/d calcium plus vitamin D3 placebo; (3) 50,000 IU/wk vitamin D3 (equal to 7143 IU/d) plus 1000 mg/d calcium; or (4) vitamin D3 placebo plus calcium placebo for 8 weeks. Anthropometric measurements and blood pressure were assessed at study baseline and after 8 weeks of intervention., Results: A greater reduction in body mass index was observed in calcium plus vitamin D group than other groups (p = 0.03). Comparison of changes in waist circumference among 4 groups revealed no significant difference in crude model (p = 0.21) and when the effect of confounders was taken into account (p = 0.08). Calcium supplementation resulted in a significant reduction in hip circumference compared to other groups (p <0.001). Systolic blood pressure significantly decreased in the calcium plus vitamin D group compared to placebo (-7.3 ± 8.7 mmHg vs 0.5 ± 8.2 mmHg; p = 0.001). However, calcium and vitamin D supplementation had no significant effects on diastolic blood pressure., Conclusion: Calcium-vitamin D3 cosupplementation can have beneficial effect on body mass index (BMI), hip circumference, and systolic blood pressure in vitamin D-insufficient type 2 diabetics.

We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

Objective: The aim of this study was to determine whether calcium supplementation, compared with placebo, increases urine calcium concentrations to levels indicative of increased renal stone risk, and the role that fluid intake, as indicated by urine volume, may play in mitigating this risk., Methods: This is a secondary analysis of data from a randomized placebo-controlled trial of 500 mg/d calcium supplementation to prevent bone loss. Subjects were 240 white postmenopausal women age 40 to 70 years in good general health. Effects of supplementation on 1-year changes in 24h urine calcium concentration and urine volume were examined., Results: Both treatment group and urine volume were strong independent predictors of urine calcium concentration (p < 0.001). Among subjects with urine volume under 2 L/24 h, more than half of placebo subjects were at lowest risk for renal stones compared with less than 35% of calcium-supplemented subjects. Among those with higher urine volumes, all placebo subjects and more than 80% of calcium supplemented subjects were at lowest risk., Conclusions: The increased risk of renal stones with calcium supplement use may be largely eliminated with adequate fluid intake, but older adults may not spontaneously consume adequate fluids to minimize this risk and should be counseled to do so.

Context: To the best of our knowledge, no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics., Objective: This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes., Methods: Totally, 118 diabetic patients were enrolled in this randomized, placebo-controlled clinical trial. After matching for age, sex, body mass index, type and dose of hypoglycemic agents, and duration of diabetes, subjects were randomly assigned into 4 groups receiving the following: 1) 50000 IU/wk vitamin D + calcium placebo; 2) 1000 mg/d calcium + vitamin D placebo; 3) 50 000 IU/wk vitamin D + 1000 mg/d calcium; or 4) vitamin D placebo + calcium placebo for 8 weeks. Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention., Results: Calcium (changes from baseline: -75 ± 19 ng/ml, P = .01) and vitamin D alone (-56 ± 19 ng/mL, P = .01) and joint calcium-vitamin D supplementation (-92 ± 19 ng/mL, P = .01) resulted in a significant reduction in serum leptin levels compared with placebo (-9 ± 18 ng/mL). This was also the case for serum IL-6, such that calcium (-2 ± 1 pg/mL, P < .001) and vitamin D alone (-4 ± 1 pg/mL, P < .001) and their combination (-4 ± 1 pg/mL, P < .001) led to significant reductions compared with placebo (3 ± 1 pg/mL). After adjustment for potential confounders, individuals in the calcium (-3.1 ± 1.3, P < .05), vitamin D (-3.1 ± 1.3, P < .05), and joint calcium-vitamin D groups (-3.4 ± 1.3, P < .05) had greater reductions in serum TNF-α concentrations compared with placebo (0.1 ± 1.2). Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels (-1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL, P = .09)., Conclusion: Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

Objective: To investigate the effect of Lithothamnium sp (LTT) supplement, a calcium-rich alga widely used for mineral reposition, on strain-induced (orthodontic tooth movement [OTM]) and infection-induced bone resorption (periodontal disease [PD]) in mice., Materials and Methods: Mice were divided into two bone resorption models: one with an orthodontic appliance and the other with PD induced by the oral inoculation of Aggregatibacter actinomycetencomitans (Aa). Both groups were fed a regular diet (vehicle), LTT-rich diet (LTT), or calcium-rich diet (CaCO3). Alveolar bone resorption (ABR), the number of osteoclasts, and the levels of tumor necrosis factor α (TNF-α), calcium, and vitamin D3 were evaluated., Results: The number of osteoclasts was reduced in LTT and CaCO3 mice, which led to diminished OTM and infection-induced alveolar bone loss. In addition, LTT- and calcium-treated groups also presented decreased levels of TNF-α in periodontal tissues and increased levels of calcium in serum., Conclusions: These results indicate that the LTT supplement influences ABR, probably due to its calcium content, by affecting osteoclast function and local inflammatory response, thus modulating OTM and PD.

Vitamin D deficiency has been implicated in the aetiology of infectious diseases and metabolic syndrome. These diseases are prevalent in the African and Asian-Indian populations of South Africa; however, there is limited data on 25-hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the present study was to assess the vitamin D status and its predictors in healthy adults in Johannesburg. We assessed the vitamin D status of 730 adult African and Asian-Indian subjects residing in Johannesburg. The contributions of sun exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat distribution to 25(OH)D concentrations were assessed. The concentrations of 25(OH)D were measured by HPLC. The contribution of 25(OH)D₃ to total 25(OH)D concentrations was assessed. The mean age of the subjects was 42·6 (SD 13·1) years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28·6 % of the Asian-Indian subjects in comparison with 5·1 % of the African subjects (P< 0·0001). Parathyroid hormone (PTH) concentrations were negatively associated with 25(OH)D concentrations, while season and sun exposure were positive predictors explaining 16 % of the variance in 25(OH)D concentrations (P< 0·0001) in the African subjects. In the Asian-Indian subjects, PTH concentrations were negatively associated with 25(OH)D concentrations, while male sex, season and Ca supplementation were positive predictors and explained 17 % of the variance in 25(OH)D concentrations (P< 0·0001). In the multivariate regression analysis, neither total body fat nor body fat distribution was predictive of 25(OH)D concentrations in either group. In conclusion, factors such as sun exposure, dietary supplement use and ethnicity are important determinants of plasma 25(OH)D concentrations.

Objective: The aim of this study was to determine the effect of combined calcium and iron versus single iron supplementation on iron status in Bolivian schoolchildren., Methods: Children ages 6 to 10 y old (N = 195), were randomly assigned to receive either 700 mg Ca (as calcium carbonate) plus 30 mg Fe (as ferrous sulfate) (Ca + Fe group) or 30 mg Fe (as ferrous sulfate) (Fe group). The doses were administered daily, from Monday to Friday, between meals at school over 3 mo. Iron status was assessed at baseline and after intervention. Additionally, overall nutritional status was assessed by anthropometry and an estimation of dietary intake., Results: At baseline, the prevalence of anemia in the Ca + Fe group and the Fe group were 15% and 21.5%, respectively. After 3 mo follow-up, the prevalence of iron deficiency anemia dropped significantly (P < 0.001) to 3% in both groups (χ(2) = NS). Iron dietary intake was within recommended levels, but calcium intake only covered 39% of the Recommended Daily Intake., Conclusion: Combined calcium and iron supplementation is equally as effective as single iron supplementation in reducing the prevalence of iron deficiency anemia in Bolivian school children., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The aim of the present study was to evaluate the potential of calcium supplementation from Lithothamnium muelleri algae on metabolic and inflammatory parameters in mice with increased adiposity. Male mice were fed and divided during 8 weeks in: control (C), a high refined carbohydrate-containing diet (HC), HC diet supplemented with 1% of Lithothamnion muelleri algae (HC + A) and HC diet supplemented with 0.9% calcium carbonate (HC + C). Animals fed HC diet had increased body weight gain and adiposity, serum glucose and cholesterol, glucose intolerance and decreased insulin sensitivity, compared to control diet. However, the HC + A and HC + C groups did not prevent these aspects and were not able to change the CD14 + cells population in adipose tissue of animals fed HC diet. Calcium supplementation with Lithothamnium muelleri algae and calcium carbonate had no protective effect against the development of adiposity, metabolic and inflammatory alterations induced by HC diet.