A maternal brain hormone that builds bone.

In lactating mothers, the high calcium (Ca2+) demand for milk production triggers significant bone loss1. Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor 3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARCKISS1) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARCKISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARCKISS1 neurons coincident with lactation. After reducing CCN3 in ARCKISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

BACKGROUND: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions. METHODS: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process. RESULTS: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all). CONCLUSIONS: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility. TRIAL REGISTRATION: ChiCTR2100048238 in the Chinese Clinical Trial Registry.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Calcium supplementation for people with overweight or obesity.

BACKGROUND: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity. MAIN RESULTS: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I2 = 97%; 12 studies, 812 participants). AUTHORS' CONCLUSIONS: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition.

Effect of vitamin D, calcium, or combined supplementation on fall prevention: a systematic review and updated network meta-analysis.

BACKGROUND: The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls. METHODS: Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I2 statistic, and publication bias was assessed using funnel plots, Begg's test, and Egger's tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I2 = 11%) among the included studies. Vitamin D supplementation at 800-1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74-0.95). In addition, 800-1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800-1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800-1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64-0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800-1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52-0.86) but not in individuals with > 50 nmol/L 25(OH)D. CONCLUSION: Vitamin D supplementation at 800-1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency.

Hypoparathyroidism after total thyroidectomy: reactive to symptoms supplementation.

INTRODUCTION: After total thyroidectomy (TT), postoperative hypoparathyroidism (PH) is the most frequent complication. Yet, management strategies for PH remain disputed. The aim of this study was to evaluate outcomes of a reactive supplementation in case of symptomatic PH. Additionally, risk factors for symptomatic PH and readmission due to PH were analyzed. MATERIALS AND METHODS: All consecutive patients who underwent TT or completion from 2017 to 2022 were considered for inclusion. During this period, a reactive to symptom vitamin-calcium supplementation was used. The primary outcome was the occurrence of severe PH after discharge resulting in readmission. RESULTS: Overall, 307 patients were included, of which 98 patients (31.9%) developed symptomatic PH including 43 patients before discharge. Independent risk factors for developing symptomatic PH were age (p = 0.010) and postoperative day 1 (POD1) PTH level (p < 0.001). Overall, 264 patients (86%) did not present PH before discharge and were discharged home. Among them, 55 patients (20.8%) experienced symptomatic PH, requiring readmission in 18 patients. The overall readmission rate owing to symptomatic PH requiring intravenous supplementation despite oral vitamin-calcium supplementation was 6.8% (n = 18). Independent risk factors for symptomatic PH-related readmission were age (p = 0.007) and POD1 PTH level (p < 0.001). Adequate cut-off values for predicting readmission were POD1 albumin-adjusted calcium = 2.1 mmol/l (Sensibility = 0.95, Specificity = 0.30) and POD1 PTH = 11.5 pg/ml (Sensibility = 0.90, Specificity = 0.71). CONCLUSION: Supplementing only symptomatic patients was safe and efficient. This attitude does not alter on morbidity, mortality or readmission rate which is in line with current literature.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years. Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up. Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Successful Localization by Hyperselective Arterial Calcium Injection Test for Surgical Resection of Insulinoma: A Case Report.

Surgery is the main treatment for insulinoma, and precise preoperative localization is important to determine the extent of resection and to rule out multiple lesions. The selective arterial calcium injection (SACI) test is instrumental in the localization of insulinoma. Here we report a patient in whom the exact location of pancreatic insulinoma could not be determined by the conventional SACI test, and thus surgery was replaced with oral diazoxide. The hyperselective SACI test subsequently localized the lesion accurately, allowing surgical resection of the pancreatic body and tail while preserving the pancreatic head. We recommend the use of the hyperselective SACI test when the conventional SACI test fails to accurately determine the location of insulinoma lesions within the pancreas.

Pre-eclampsia.

Pre-eclampsia is a multisystem pregnancy disorder characterised by variable degrees of placental malperfusion, with release of soluble factors into the circulation. These factors cause maternal vascular endothelial injury, which leads to hypertension and multi-organ injury. The placental disease can cause fetal growth restriction and stillbirth. Pre-eclampsia is a major cause of maternal and perinatal mortality and morbidity, especially in low-income and middle-income countries. Prophylactic low-dose aspirin can reduce the risk of preterm pre-eclampsia, but once pre-eclampsia has been diagnosed there are no curative treatments except for delivery, and no drugs have been shown to influence disease progression. Timing of delivery is planned to optimise fetal and maternal outcomes. Clinical trials have reported diagnostic and prognostic strategies that could improve fetal and maternal outcomes and have evaluated the optimal timing of birth in women with late preterm pre-eclampsia. Ongoing studies are evaluating the efficacy, dose, and timing of aspirin and calcium to prevent pre-eclampsia and are evaluating other drugs to control hypertension or ameliorate disease progression.

Metabolomics in liver injury induced by dietary cadmium exposure and protective effect of calcium supplementation.

The purpose of the study was to explore the effect of calcium (Ca) supplementation on liver injury induced by cadmium (Cd) in rats and its potential metabolic mechanisms through metabolomics analysis. Seventy rats were randomly allotted into 7 groups, including a control group, 3 groups with different levels of Cd exposed (1, 5, and 50 mg Cd/kg diet), and 3 corresponding Ca supplement groups (4 g Ca/kg diet) based on the Cd exposed groups. Dietary intake was simulated by giving Cd or Cd+Ca in the diets of rats. After 13-week feeding, serum biochemical parameters and liver histopathology were examined. Then the metabolic analysis of rat liver tissues was performed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS). It was demonstrated that Ca supplementation could reverse the abnormal alterations in TG, TC, GSH, MDA induced by Cd exposure, as well as the hepatic pathological changes in rats. Furthermore, the metabolomics analysis of liver samples revealed several distinct regulatory pathways, including energy, amino acid, and lipid metabolic pathways. In conclusion, it showed that Ca supplementation had an ameliorative effect on liver injury induced by Cd exposure in rats, which may be related to the role of Ca in regulating multiple metabolic pathways.

The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial.

Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD.Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured.Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p = 0.008). The effect of vitamin D on the PPD score was larger when vitamin D was given alone than given together with calcium (p = 0.042 and p = 0.004, respectively). No significant differences in estradiol, IL6 and TNFα were observed between the three groups.Discussion: Vitamin D may be effective in improving the clinical symptoms of PPD; however, the mechanism of the effect might not entirely operate through inflammatory and/or hormonal changes.

Nutritional Approaches as a Treatment for Impaired Bone Growth and Quality Following the Consumption of Ultra-Processed Food.

The severe impairment of bone development and quality was recently described as a new target for unbalanced ultra-processed food (UPF). Here, we describe nutritional approaches to repair this skeletal impairment in rats: supplementation with micro-nutrients and a rescue approach and switching the UPF to balanced nutrition during the growth period. The positive effect of supplementation with multi-vitamins and minerals on bone growth and quality was followed by the formation of mineral deposits on the rats' kidneys and modifications in the expression of genes involved in inflammation and vitamin-D metabolism, demonstrating the cost of supplementation. Short and prolonged rescue improved trabecular parameters but incompletely improved the cortical parameters and the mechanical performance of the femur. Cortical porosity and cartilaginous lesions in the growth-plate were still detected one week after rescue and were reduced to normal levels 3 weeks after rescue. These findings highlight bone as a target for the effect of UPF and emphasize the importance of a balanced diet, especially during growth.

Regional Citrate Anticoagulation for Continuous Kidney Replacement Therapy With Calcium-Containing Solutions: A Cohort Study.

OBJECTIVE: Regional citrate anticoagulation (RCA) is the preferred anticoagulation method for continuous kidney replacement therapy (CKRT) recommended by KDIGO. Limited availability of calcium-free solutions often imposes challenges to the implementation of RCA for CKRT (RCA-CKRT). The principal purpose of this study was to characterize the outcomes of RCA-CKRT using calcium-containing solutions. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We evaluated the safety and efficacy of RCA-CKRT with calcium-containing dialysate and replacement fluid used for 128 patients. A total of 571 filters and 1,227 days of CKRT were analyzed. EXPOSURES: Liver disease, sepsis in the absence of liver disease, and sepsis with liver disease. OUTCOMES: Filter life and metabolic complications per 100 CKRT days. ANALYTICAL APPROACH: Linear mixed-effects model and generalized linear mixed-effects models. RESULTS: The majority of patients were male (91; 71.1%), 32 (25%) had liver disease, and 29 (22.7%) had sepsis without liver disease. Median filter life was 50.0 (interquartile range, 22.0-118.0) hours, with a maximum of 322 hours, and was significantly lower (33.5 [interquartile range, 17.5-60.5] h) in patients with liver disease. Calcium-containing replacement solutions were used in 41.6% of all CKRT hours and reduced intravenous calcium requirements by 31.7%. Hypocalcemia (ionized calcium<0.85mmol/L) and hypercalcemia (total calcium>10.6mg/dL) were observed in 6.0 and 6.7 per 100 CKRT days, respectively. Citrate accumulation was observed in 13.3% of all patients and was associated with metabolic acidosis in 3.9%, which was not significantly different in patients with liver disease (9.3%; P = 0.2). LIMITATIONS: Lack of control groups that used calcium-free dialysate and replacement solutions with RCA-CKRT. Possible overestimation of filter life from incomplete data on cause of filter failure. CONCLUSIONS: Our study suggests that RCA-CKRT with calcium-containing solutions is feasible and safe in critically ill patients, including those with sepsis and liver disease.

Calcium Intake and Iron Status in Human Studies: A Systematic Review and Dose-Response Meta-Analysis of Randomized Trials and Crossover Studies.

BACKGROUND: The interaction between dietary (and supplementary) divalent ions has been a long-standing issue in human nutrition research. Developing an optimal calcium and iron supplementation recommendation requires detailed knowledge of the potential trade-offs between: 1) the clinical effects of concurrent intake on iron absorption and hematological indices; and 2) the potentially negative effects of separated ingestion on adherence to iron and/or calcium supplements. Human clinical studies have examined the effects of calcium intake on iron status, but there are no meta-analyses or recent reviews summarizing the findings. OBJECTIVES: To synthesize peer-reviewed, human, randomized, and cross-over studies on effects of calcium consumption on iron indices without age, gender, or any other restrictions. METHODS: Weighted mean differences for total, heme, and nonheme iron absorption (%) and serum ferritin (µg/L) were obtained from pooled analysis of the highest daily calcium intake compared to the lowest daily calcium intake. RESULTS: The negative effect of calcium intake was statistically significant in short-term iron absorption studies, but the effect magnitude was low [weighted mean difference (WMD) = -5.57%; 95% CI: -7.09 to -4.04]. The effect of calcium on the iron status was mixed. The inverse dose-response association of calcium intake with the serum ferritin concentration was significant (P value = 0.0004). There was, however, no reduction in the hemoglobin concentration (WMD = 1.22g/L;  95% CI:  0.37-2.07). CONCLUSIONS: The existing body of studies is insufficient to make recommendations with high confidence due to heterogeneity in designs, limitations of ferritin as an iron biomarker, and a lack of intake studies in pregnant women. Prescribing separation of prenatal calcium and iron supplements in free-living individuals is unlikely to affect the anemia burden. There is a need for effectiveness trials comparing the effects of prescribing separated intake to concurrent intake, with functional endpoints as primary outcomes and adherence to each supplement as intermediate outcomes.

Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.

BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.

Diet-gene interaction: effects of polymorphisms in the ACE, AGT and BDKRB2 genes and the consumption of sodium, potassium, calcium, and magnesium on blood pressure of normotensive adult individuals.

Functional variants in genes of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems have already been implicated in blood pressure (BP) modulation, but few studies have focused on a nutrigenetics approach. Thus, the aim of this study is to verify the effects of the interaction between genetic polymorphisms (rs4340-ACE, rs699-AGT, and rs1799722-BDKRB2) and micronutrient consumption (sodium, potassium, calcium, and magnesium) on BP values of normotensive adult individuals. The study included 335 adults, men and women, 25.5 (6.6) years old. Biochemical, anthropometric, BP measurements, and food intake data were assessed for all participants. Gene-nutrient interaction on BP outcome was tested by multiple linear regression with manual backward stepwise modeling. Our results indicated that individuals with G allele for rs699 polymorphism, in the increase of sodium and magnesium consumption, both in the genotypic model (sodium, p = 0.035; magnesium, p = 0.016) and in the dominant model (sodium, p = 0.009; magnesium, p = 0.006) had higher systolic BP (SBP) levels compared to AA homozygotes (sodium, p = 0.001; magnesium, p < 0.001). Also, individuals with the T allele for the rs1799722 polymorphism, with higher calcium intake, had significantly higher levels of SBP and diastolic BP (DBP) when compared to CC homozygotes (p = 0.037). In conclusion, our findings pointed for significant interactions between genetic polymorphisms (rs699-AGT and rs1799722-BDKRB2) and the consumption of micronutrients (sodium, magnesium, and calcium) on the BP variation. These findings contribute to the understanding of the complex mechanisms involved in BP regulation, which probable include several gene-nutrition interactions.

Thresholds of Basal- and Calcium-Stimulated Calcitonin for Diagnosis of Thyroid Malignancy.

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.