Calcium (Citrate)

OBJECTIVE: To perform a meta-analysis of data from available published trials comparing the bioavailability of calcium carbonate with that of calcium citrate. DATA SOURCES: The whole set was comprised of 15 studies involving 184 subjects who underwent measurement of calcium absorption from calcium carbonate and calcium citrate. Category A excluded four studies for lack of physiological relevance, use of a mixed preparation with low content of calcium carbonate, or wide variability in results. Category B was comprised of five studies (from Category A) involving 71 subjects who took calcium supplements on an empty stomach. Category C was comprised of six studies (from Category A) involving 65 subjects who took calcium preparations with meals. METHOD: The meta-analysis of calcium absorption data from calcium carbonate and calcium citrate, with calculation of effect size and 95% confidence intervals. RESULTS: Calcium absorption from calcium citrate was consistently significantly higher than that from calcium carbonate by 20.0% in the whole set, by 24.0% in Category A, by 27.2% on an empty stomach, and by 21.6% with meals. CONCLUSION: Calcium citrate is better absorbed than calcium carbonate by approximately 22% to 27%, either on an empty stomach or co-administered with meals.

OBJECTIVE: This study compared the efficacy of calcium (Ca) citrate and Ca carbonate supplementation on Ca absorption following Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and one-anastomosis gastric bypass (OAGB) surgeries. SETTING: A single specialized bariatric center. METHODS: A randomized, double-blinded, crossover study between October 2023 and February 2024. One hundred fifty participants 6 months postmetabolic bariatric surgery (MBS) were randomly selected from the electronic patient record system to create a pool of patients to randomize for the study. The intestinal absorption of Ca carbonate and Ca citrate among groups divided by surgical procedure was compared over 8 hours of testing. Measurements included serum and urine Ca concentrations for peak values (Cmax) and area under the curve (AUC0-8h), along with parathyroid hormone (PTH) levels to calculate minimum PTH (PTHmin) and cumulative PTH decline (AUC0-8h). RESULTS: In total, 50 per each surgery group were included with an average age of 40.5 ± 7.6 years, of whom 128 (85.3%) were female. The participants' average BMI was 30.3 ± 2.0 kg/m2. The average time elapsed after MBS was 9.8 ± 1.0 months. Ca citrate intake significantly lowered PTH levels and showed enhanced relative Ca bioavailability compared to Ca carbonate. Specifically, PTH levels were notably reduced from 3 to 6 hours postadministration with Ca citrate, with significant differences (P < .001). Ca citrate also demonstrated superior relative bioavailability, as evidenced by a higher AUC0-8h of 76.1 mg/dL·h versus 74.7 mg/dL·h for carbonate (P = .001) and a Cmax of 9.8 mg/dL compared to 9.5 mg/dL for carbonate (P < .001). Additionally, urinary Ca excretion over 9 hours was significantly greater in the citrate group at 83.7 mg/dL compared to 68.6 mg/dL for carbonate (P < .001). CONCLUSION: The study demonstrates that Ca citrate was significantly better than carbonate in reducing PTH levels, enhancing relative Ca bioavailability, and increasing urinary Ca excretion. Additionally, Ca citrate resulted in higher cumulative urinary Ca excretion, indicating better Ca absorption.

INTRODUCTION: Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET. PURPOSE: We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program. METHODS: Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA). RESULTS: MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70). CONCLUSIONS: SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state.

BACKGROUND: Previous studies have reported that vitamin D supplement could improve fracture healing, but evidence regarding the role of vitamin D supplements in spinal fusion was limited. Thus, this study aimed to evaluate the effectiveness of oral vitamin D supplements on fusion outcomes in patients undergoing lumbar spinal fusion. METHODS: This randomized, double-blind, parallel-designed, active-control trial included the patients who planned for elective lumbar spinal fusion. Eligible patients were randomly assigned to receive either daily vitamin D3 (cholecalciferol) 800 IU and daily calcium citrate 600 mg (experimental group) or only daily calcium citrate 600 mg (control group). All supplements were given from postoperative day 1 and lasted for 3 months. Primary outcome was postoperative 1-year fusion rate, and secondary outcomes included time to fusion, Oswestry Disability Index (ODI), and visual analogue scale (VAS) for pain. RESULTS: Among the included 34 patients (21 in the experimental group and 13 in the control group), baseline 25-hydroxyvitamin D (25[OHVitD) level was 26.7 (10.4) ng/ml. Preoperative prevalence of vitamin D deficiency and insufficiency were 23.5% and 47.1%, respectively. Postoperative 1-year fusion rate was not significantly different between the two groups (95.2% vs. 84.6%, P = 0.544). The experimental group had significantly shorter time to fusion (Kaplan-Meier estimated: 169 days vs. 185 days [interquartile range: 88-182 days vs. 176-324 days], log-rank test: P = 0.028), lower postoperative 6-month ODI (P < 0.001), and lower postoperative 6-month VAS (P < 0.001) than the control group. Time to fusion was significantly and negatively correlated with preoperative, postoperative 3-month, and 6-month 25(OH)VitD levels (all P < 0.01). CONCLUSION: The patient with vitamin D supplements had shorter time to fusion, better spinal function and less pain after elective spinal fusion. Further research is warranted to identify the patients who can benefit the most from vitamin D supplements and the appropriate dose of vitamin D supplements. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05023122. Registered 20 August 2021. Retrospectively register

OBJECTIVE: To investigate if the gout-protective effect of low-fat dairy products could be attributed to the urate-lowering effect of calcium. METHODS: This is a placebo-controlled trial in which thirty-five adult (aged 18-42 years) female low-calcium consumers (<800 mg/d) were randomized to one of three treatment groups: low calcium breakfast (control, ∼70 mg of calcium/d) -C or high-calcium breakfast (∼770 mg/d) from calcium citrate - CIT or from skim milk - SM, during 45 consecutive days. Breakfasts were matched for potential confounders and were provided as part of an energy-restricted normoprotein diet containing an additional 800 mg of calcium/d. Dual-energy X-ray absorptiometry measurements (body fat assessment) and fasting blood samples (urate, ionic calcium, PTH, and 1,25-(OH)2-D3) were taken at baseline and the end of the experiment. CLINICAL TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br/ (RBR-7Q2N33). RESULTS: Despite no significant changes in total body weight/fat, CIT and SM led to a significant reduction in serum urate and ionic calcium, but did not affect PTH and vitamin D concentrations compared to C. CIT and SM reduced baseline serum urate by ∼14% and ∼17%, respectively. There was a trend to a positive correlation between changes in serum urate and changes in ionic calcium on day 45 (r = 0.327, P = 0.055). CONCLUSIONS: Calcium supplementation (770 mg/d from dairy or calcium citrate) reduced serum urate concentrations, suggesting that the gout-protective effect of low-fat dairy consumption is at least partly due to a urate-lowering effect of calcium.

Comment in J Bone Miner Res. 2023 Mar;38(3):451. doi: 10.1002/jbmr.4692. In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by

BACKGROUND: Hypovitaminosis D is associated with Sarcopenic Obesity (SO), but evidence from randomized Vitamin D 3 (VD3) trials is scarce. OBJECTIVE: Compare the effect of VD3 supplementation, at two doses, on SO indices at 12 months. METHODS: Overweight older adults (>65 years) with baseline 25-hydroxyvitamin D (25OHD) of 10-30 ng/mL were recruited in this double-blind, randomized, controlled multicenter trial (clinicaltrial.gov identifier: NCT01315366). All subjects received 1000 mg calcium citrate/day and underwent total body Dual-energy X-ray Absorptiometry for body composition assessment. Low Dose Group (LDG) and High Dose Group (HDG) received 600 IU -Institute of Medicine (IOM) Recommended Dietary Allowance (RDA)- and 3750 IU VD3/day, respectively. RESULTS: Mean age was 71 ± 4.6 years, 55% females, BMI: 30.2 ± 4.5 Kg/m2, and 43% had metabolic syndrome. There were no differences in baseline characteristics between groups. At 12 months, 248 participants had body composition data, 122 in LDG and 126 in HDG. Proportions of patients with diminished muscle mass, muscle strength, and visceral adiposity did not differ between the 2 groups at baseline or 12 months. Similarly, no significant differences were noted in the proportion of patients with SO at study entry (1.8% in LDG vs 1.6% HDG; p = 0.99) and at 12 months (3.7% in LDG vs. 0.9% HDG; p = 0.18) across arms. CONCLUSIONS: Weekly VD3, at the daily equivalent of 3750 IU/day, did not improve indices of sarcopenia nor adiposity compared to the IOM RDA dose in adults. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

CONTEXT: Guidelines for the dosage of vitamin D supplementation vary widely globally. OBJECTIVE: To investigate the impact of 2 vitamin D doses, bracketed between the IOM recommended dietary allowance (RDA) and the upper tolerable limit, on vitamin D nutritional status in elderly individuals. METHODS: This post hoc analysis of data collected from a 12-month, double-blind, randomized control trial included 221 ambulatory participants (≥ 65 years) with a mean BMI of 30.2 kg/m2 and a mean baseline serum 25-hydroxyvitamin D [25(OH)D] level of 20.4 ± 7.4 ng/mL, who were recruited from 3 outpatient centers in Lebanon. All participants received 1000 mg of elemental calcium daily from calcium citrate plus the daily equivalent of either 600 IU or 3750 IU of vitamin D3. RESULTS: Mean 25(OH)D level at 12 months was 26.0 ng/mL with low dose and 36.0 ng/mL with high dose vitamin D3. The proportion of participants reaching a value ≥ 20 ng/mL was 86% in the low dose, and 99% in the high dose arms, with no gender differences. The increment of 25(OH)D per 100 IU/day was 1 ng/mL with the low dose, and 0.41 ng/mL with the high dose. Serum 25(OH)D levels at 1 year were highly variable in both treatment arms. Baseline 25(OH)D level and vitamin D dose-but not age, BMI, gender, or season-were significant predictors of serum 25(OH)D level post-intervention. CONCLUSION: The IOM Recommended Dietary Allowance (RDA) of 600 IU/day does not bring 97.5% of ambulatory elderly individuals above the desirable threshold of 20 ng/mL. Country-specific RDAs are best derived taking into account the observed variability and predictors of achieved 25(OH)D levels. © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

INTRODUCTION: Resistance exercise training (RET) induces muscle hypertrophy that, when combined with co-temporal protein ingestion, is enhanced. However, fewer studies have been conducted when RET is combined with multi-ingredient supplements. PURPOSE: We aimed to determine the effect of a high-quality multi-ingredient nutritional supplement (SUPP) versus an isonitrogenous (lower protein quality), isoenergetic placebo (PL) on RET-induced gains in lean body mass (LBM), muscle thickness, and muscle cross-sectional area (CSA). We hypothesized that RET-induced gains in LBM and muscle CSA would be greater in SUPP versus PL. METHODS: In a double-blind randomized controlled trial, 26 (13 male, 13 female) healthy young adults (mean ± SD, 22 ± 2 yr) were randomized to either the SUPP group (n = 13; 20 g whey protein, 2 g leucine, 2.5 g creatine monohydrate, 300 mg calcium citrate, 1000 IU vitamin D) or the PL group (n = 13; 20 g collagen peptides, 1.4 g alanine, 0.6 g glycine) groups, ingesting their respective supplements twice daily. Measurements were obtained before and after a 10-wk linear progressive RET program. RESULTS: Greater increases in LBM were observed for SUPP versus PL (SUPP: +4.1 ± 1.3 kg, PL: +2.8 ± 1.7 kg, P < 0.05). No additive effect of the supplement could be detected on vastus lateralis muscle CSA, but SUPP did result in increased biceps brachii muscle CSA and thickness (P < 0.05). CONCLUSIONS: We conclude that when combined with RET, the consumption of SUPP increased LBM and upper-body CSA and thickness to a greater extent than to that observed in the PL group of healthy young adults.

BACKGROUND: The purpose of this study was to examine the effect of probiotics and prebiotics (LactoWise®) on weight loss, blood pressure, and clinical lab values in morbidly obese patients undergoing laparoscopic sleeve gastrectomy (LSG). MATERIALS METHODS: Sixty patients undergoing LSG were recruited to participate in the study and randomized into either a LactoWise® or placebo group. The LactoWise® group (LWG) received 4.5 billion live cells of bacillus coagulans and galactomannans (300 mg); the placebo group received 600 mg of calcium citrate yielding 126 mg of elemental calcium. Both groups took their assigned capsule daily for 3-months post-surgery. Standard clinical lab values were measured pre-surgery and at 3-months post-surgery. Weight and blood pressures were measured at baseline, 2 weeks, 6 weeks, and 3 months post-surgery. RESULTS: A total of 35 patients with a mean age of 47.7 ± 12.4 years and a mean body mass index (BMI) of 46.6 ± 8.2 kg/m2 completed the study. There was a significant difference in BMI at baseline between the two study groups (43.0 ± 7.0 vs. 49.2 ± 8.3, P = .02). Weight loss was greater in the LWG compared to placebo at 6 weeks but showed no significant difference at 3 months post-op. In addition, there was a significant drop in triglycerides (TG) (P = .02) over time in the LWG (P = .01). The LWG had a significant decrease in AST and LDL compared to the placebo group (P = .03). CONCLUSION: Bariatric surgery (BS) produces positively impacting metabolic results in morbidly obese patients. Our study shows that in the case of triglycerides, LDL, weight loss and AST, administering of a probiotic/prebiotic blend may play a role in improving clinical outcomes of morbidly obese patients undergoing LSG.

The effectiveness of oral calcium (Ca) may be contingent on a patient׳s factors beyond compliance, such as proton-pump inhibitor use and the choice of calcium supplements. A 32-year-old Hispanic male with end-stage renal disease on peritoneal dialysis underwent successful surgical parathyroidectomy (intact parathyroid hormone level: 2,328pg/mL; postsurgical: 287-69pg/mL [normal: 8.5-72.5]). His postoperative course was complicated by severe and recurrent hypocalcemia as outpatient and he needed repeated admissions for intravenous Ca gluconate. Initially, severe hypocalcemia (corrected Ca: 4.8-5.6mg/dL; nadir ionized Ca: 0.57-0.69mmol/L) was attributed solely to medical noncompliance with oral Ca carbonate (3750mg, 3×/day between meals) and calcitriol (2-4mcg/day). Recognizing coexisting treatment with proton-pump inhibitor, oral Ca supplement was changed to calcium citrate (2,850mg, 3×/day) with prompt resolution of hypocalcemia (corrected Ca: 8.1-8.3mg/dL). This current case and the included literature review emphasize the disproportionate effectiveness of Ca citrate in subjects with achlorhydria.

CONTEXT: Vitamin D is often recommended for use with calcium supplements to increase absorption. There are no systematic studies of vitamin D on calcium absorption that indicate what dose should be recommended. OBJECTIVE: Our objective was to study the effect of increasing doses of vitamin D3 on calcium absorption. DESIGN AND SETTING: We conducted a randomized double-blind placebo-controlled trial at Creighton University Medical Center, Omaha, NE. PARTICIPANTS: Participants included 163 postmenopausal Caucasian women with vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) below 20 ng/ml (50 nmol/liter). INTERVENTION: Participants were randomized to receive one of the vitamin D3 doses, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d, or placebo for 1 yr. Calcium intake was increased to 1200-1400 mg daily by giving daily calcium citrate. MAIN OUTCOME: We evaluated the change in calcium absorption on vitamin D. RESULTS: Mean serum 25OHD increased from baseline 15.6 ng/ml (39 nmol/liter) to 46.5 ng/ml (112 nmol/liter) in subjects randomized to the highest dose of vitamin D (4800 IU). Calcium absorption was more significantly related to serum 25OHD (R2=0.50; P=0.001) than dose (R2=0.47; P=0.033). Calcium absorption of a 100-mg dose increased from 52-58% (6 mg) over a serum 25OHD range of 20-66 ng/ml (50-165 nmol/liter). CONCLUSIONS: There was no evidence of a threshold for reduced calcium absorption in the serum 25OHD range of 10-66 ng/ml (25-165 nmol/liter). The increase in absorbed calcium of 6% on high doses of vitamin D is so small that the same amount could be obtained from half a glass of milk (100 ml) or 100 mg elemental calcium. The results challenge assumptions about the value of adding vitamin D to increase calcium absorption except when serum 25OHD is very low that is less than 10 ng/ml (25 nmol/liter).

BACKGROUND: Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption. MATERIALS AND METHODS: The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs. RESULTS: Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone. CONCLUSIONS: Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations.

BACKGROUND: Hypothyroidism and hypocalcemia are common after thyroid and parathyroid surgery. In this article, the authors provide clinically-oriented recommendations to help surgeons, general practitioners, internists, and endocrinologists give their affected patients adequate hormone replacement therapy. METHODS: Selective evaluation of original articles and reviews that were retrieved by a PubMed search over the years 1980 to 2010, as well as of the recommendations of medical societies including the Endocrine Society (USA), the German Society for Endocrinology (Deutsche Gesellschaft für Endokrinologie), and the American and European Thyroid Associations. RESULTS: Important issues in L-thyroxine replacement therapy include: the selection of the hormone preparation (T4 or T4/T3), combination with iodine (yes/no), the definition of therapeutic TSH ranges (particularly after surgery for thyroid cancer), the extent of remaining thyroid tissue after goiter surgery and its significance, underlying diseases, and drug interactions. The major issues in the treatment of postoperative hypoparathyroidism are: the selection of suitable calcium and vitamin D preparations, the definition of therapeutic goals, the treatment of hypercalciuria and hyperphosphatemia, and the option of recombinant parathormone therapy. CONCLUSION: Effective treatment requires an appropriate choice of medication and an understanding of its pharmacokinetics as well as of the possible effects of the patient's underlying disease, comorbidities, and other medications on its absorption and metabolism.

Comment in Eur Urol. 2007 May;51(5):1445. doi: 10.1016/j.eururo.2007.02.023. Calcium oxalate monohydrate (COM), which represents a major component of kidney stones, is an end metabolite of ethylene glycol. COM accumulation has been linked with acute renal toxicity in ethylene glycol poisoning. COM injures the kidney either by directly producing cytotoxicity to the kidney cells or by aggregating in the kidney lumen leading to the blockage of urine flow. The present studies were designed to examine whether aluminum citrate could reduce the toxicity of COM. Toxicity was determined in human proximal tubule cells by leakage of lactate dehydrogenase or uptake of ethidium homodimer and in erythrocytes by degree of hemolysis. Aluminum citrate significantly inhibited the leakage of lactate dehydrogenase from human proximal tubule cells and protected against cell death from COM. The inhibitory effect of aluminum citrate was greater than that of other citrate or aluminum salts such as sodium citrate, aluminum chloride, calcium citrate, ammonium citrate or potassium citrate. Aluminum citrate significantly inhibited the aggregation of COM crystals in vitro and decreased red cell membrane damage from COM. Aluminum citrate appeared to directly interact with COM, but not with the cell membrane. As such, aluminum citrate reduced the cytotoxicity by a physico-chemical interaction with the COM surface, and not by dissolving the COM crystals. These studies suggest that aluminum citrate may protect against tissue damage that occurs with high levels of oxalate accumulation, especially in ethylene glycol poisoning and possibly in hyperoxaluric states.

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

The authors hypothesized that estrogen treatment or vitamin D status may affect the bioavailability of two common calcium supplements differently. Using data derived from a recent trial in 25 postmenopausal women, the authors found that deltaAUC of serum calcium after subtraction of placebo was significantly higher after calcium citrate (median, 0.85; 25th to 75th percentile, 0.70 to 3.15) than after calcium carbonate (0.25; -0.58 to 1.00) in non-estrogen-treated patients. There was no difference in the bioavailability of calcium between the two calcium formulations in estrogen-treated patients. Bioavailability was also significantly higher with the citrate salt for the subgroups with lower serum 25-hydroxyvitamin D and higher serum 1,25-dihydroxyvitamin D concentrations. In summary, bioavailability of calcium from the calcium carbonate product was more dependent on estrogen treatment and vitamin D status than that of calcium citrate. This may explain the variable results of reported calcium supplementation studies.

Comment in Am J Clin Nutr. 1998 May;67(5):948-50. doi: 10.1093/ajcn/67.5.948. There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.

OBJECTIVES: The aim of this study was to determine the effect of calcium carbonate and calcium citrate on zinc absorption. DESIGN: The zinc tolerance test (ZTT), which is the plasma zinc response to an oral zinc challenge, was used to quantitate zinc absorption. A physiological test dose of zinc (4.5 mg elemental zinc as 20 mg zinc sulphate) was used. Subjects underwent ZTTs on three separate occasions, each time consuming in random order, either 4.5 mg elemental zinc, zinc with 600 mg elemental calcium as calcium carbonate or zinc with 600 mg elemental calcium as calcium citrate. SETTING: Metabolic ward conditions. SUBJECTS: Nine, free-living, healthy female subjects recruited from the University population. INTERVENTIONS: Blood samples were obtained at 30 min intervals for 4 h postdose. RESULTS: The area under the plasma zinc curve (AUC) (mean +/- SEM) following the coingestion of zinc with calcium carbonate (438.4 +/- 129.0 mumol Zn.min/100 g albumin) and calcium citrate (308.0 +/- 110.5) was significantly lower (P < 0.017) than when zinc was ingested alone (1561.7 +/- 240). Urinary excretion of calcium was significantly higher (P < 0.017) at 4 h after supplementation with calcium citrate (0.83 +/- 0.12 mumol Ca/mumol creatinine) compared with calcium carbonate (0.40 +/- 0.11). CONCLUSIONS: The decrease in zinc absorption following the ingestion of zinc with different forms of calcium suggests that an antagonistic competition occurred between the minerals and that elemental calcium is the inhibiting factor.

The effect of calcium citrate on intestinal aluminum absorption, assessed by the increment in urinary aluminum excretion, was evaluated in eight normal men. Baseline urinary aluminum excretion was determined for 2 days; thereafter, subjects ingested aluminum hydroxide for 3 days. In a cross-over study, subjects were given either calcium citrate, 950 mg four times a day, or placebo during the 3 days of aluminum hydroxide ingestion (2.4 g/d). Plasma aluminum levels were measured on the second control day and the third day of aluminum hydroxide ingestion. Baseline urinary aluminum excretion was 0.02 +/- 0.004 (6.5 +/- 1.1 micrograms/g creatinine) and 0.03 +/- 0.005 mumol/mmol creatinine (7.4 +/- 1.3 micrograms/g creatinine). These values increased during aluminum hydroxide therapy, but values were much greater when calcium citrate was ingested with aluminum hydroxide. On 3 consecutive days, urinary aluminum excretion levels were 11.1 +/- 3.23, 8.8 +/- 2.9, and 5.3 +/- 0.7 times greater during the administration of calcium citrate with aluminum hydroxide than with aluminum hydroxide alone. Plasma aluminum levels did not differ in the two treatment groups. Thus, calcium citrate markedly enhances the absorption of aluminum from aluminum hydroxide and the two must not be prescribed together in patients with renal failure.

Parathyroid hormone (PTH) is important in bariatric patients for understandingcalcium homeostasis and bone health. The effects of calcium carbonate and calcium citrate onPTH levels need further investigation in this population. This systematic review and meta-analysis of randomized clinical trials investigated the effect of calcium citrate versus calciumcarbonate on PTH levels in patients undergoing bariatric surgery, using the PRISMA guidelines. Atotal of 227 participants from four studies were included in the meta-analysis. Pooled analysisshowed no significant differences between the effect of calcium citrate versus calcium carbonateon serum calcium levels (WMD: 0.03 mg/dl, 95% CI: -0.04,0.11;I=35.7%) and PTH levels(WMD: 0 pg/ml, 95%CI: -2.81,2.82;I=73.5). Subgroup analysis showed that a single dose of calcium citrate significantly reduced PTH levels better than calcium carbonate (WMD: -1.17, 95%CI: -2.04,-0.29; I2=0%), but no significant difference was observed in chronic interventions (WMD: 2.05, 95% CI: -3.68, 7.78; I =81.4%). Furthermore, single dose of calcium citrate increased serum levels of calcium AUC (WMD: 1.28, 95% CI: 0.58, 1.99; I =0%) and calcium Cmax (WMD: 0.28, 95% CI: 0.19, 0.37; I =0%), and decreased PTH AUC (WMD: -30.65, 95% CI:-45.49, -15.81; I =0%), more than calcium carbonate. In conclusion, a single dose of calcium citrate is superior to calcium carbonate in reducing PTH levels in patients undergoing bariatric surgery, but no difference was observed over time between the formulations. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Urolithiasis (UL) is a multifactorial condition whose global prevalence has been increasing in recent years, and it is closely associated with dietary factors. Diet is one of the key elements linked to the development of UL due to the intake of many nutrients that cause metabolic alterations associated with the crystallisation process and the risk of developing urinary stones. Despite the crucial role of diet, few studies have implemented dietary interventions. In this sense, dietary modifications play a fundamental role in the prevention, control and management of UL. Thus, the aim of this systematic review is to summarise the main beneficial effects of dietary interventions in populations with UL. A comprehensive search was conducted in MEDLINE/PubMed, SpringerLink, Google Scholar, Scielo and Redalyc databases for intervention studies published up to July 2025 that reported dietary interventions aimed at preventing and controlling UL. The risk of bias and quality of studies were assessed. A total of twenty-six articles were included, focusing on dietary interventions such as controlling sodium, oxalate, calcium, citrate and protein intake, as well as low-calorie diets. In addition, foods such as lemon, orange, melon, lime, cranberry, apple juices, milk, vinegar, black seed, green bean extract, probiotics and synbiotic were also explored, which promoted significant changes in serum and urinary parameters related to UL. This review compiles evidence on dietary intervention strategies that lead to significant improvements in biochemical parameters in populations with UL (PROSPERO CRD42022361702).

PURPOSE OF REVIEW: The association of kidney stone disease (KSD) and gastrointestinal (GI) surgery has been well established. With a rising obesity crisis, we wanted to see the correlation of urinary composition in patients undergoing bariatric surgery and their risk of KSD. The objective of this paper is to perform a systematic review and meta-analysis of literature to evaluate the changes in urinary composition and risk of KSD following bariatric surgery. RECENT FINDINGS: A total of seven studies (2498 patients) underwent bariatric surgery with a mean age of 46.7 years and a male:female ratio of 1:3. The most popular bariatric surgery was the Roux-en-Y procedure. Meta-analysis of the studies showed that significant decrease in urinary calcium, citrate, and urate, and increase in urinary oxalate. There was also a nonsignificant volume reduction in the post-operative cohort. The decrease in urinary citrate and increase in urinary oxalate are both predisposing factors of stone formation. There is strong evidence that bariatric surgery results in significant changes in urine composition in keeping with the increased risk of developing KSD. This identifies useful therapeutic targets in the prophylactic management of patients who have undergone bariatric surgery. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) for investigating the effect of dietary treatment and fluid intake on the prevention of recurrent calcium stones and changes in urine composition. PubMed, Web of Science, Embase, EBSCO, and Cochrane Library databases (updated November 2020) were searched for studies with the following keywords: diet, fluid, recurrent, prevention, randomized controlled trials, and nephrolithiasis. The search strategy and study selection process was conducted by following the PRISMA statement. Six RCTs were identified for satisfying the inclusion criteria and enrolled in this meta-analysis. Our result showed that low protein with or without high fiber diet intervention does not decrease the recurrence of stone upon comparing with control groups (RR = 2.32, 95% CI = 0.42-12.85; P = 0.34) with significant heterogeneity among the studies (I2 = 81%, P = 0.02). But normal-calcium, low protein, low-salt diet had recurrences did reduced the recurrence compared to normal-calcium diet. And the fluid intake has a positive effect on prevention of recurrent stone formation (RR = 0.39, 95% CI = 0.19-0.80; P = 0.01) with insignificant heterogeneity among the studies (I2 = 9%, P = 0.30). The different components of urine at baseline were reported in four studies. Upon reviewing the low protein with or without high fiber dietary therapy groups, it was found that there were no obvious changes in the 24-hour urine sodium, calcium, citrate, urea, and sulfate. In conclusion, our study shows that the only low protein with or without fiber does not affect recurrence, but low Na, normal Ca diet has a marked effect on reducing recurrence of calcium stone. And fluid intake shows a significant reduction in the recurrence of calcium stone.

In order to develop evidence-based recommendations and expert consensus for nutrition management of patients undergoing bariatric surgery and postoperative follow-up, we conducted a systematic literature search using PRISMA methodology plus critical appraisal following the SIGN and AGREE-II procedures. The results were discussed among all members of the GARIN group, and all members answered a Likert scale questionnaire to assess the degree of support for every recommendation. Patients undergoing bariatric surgery should be screened preoperatively for some micronutrient deficiencies and treated accordingly. A VLCD (Very Low-Calorie Diet) should be used for 4-8 weeks prior to surgery. Postoperatively, a liquid diet should be maintained for a month, followed by a semi-solid diet also for one month. Protein requirements (1-1.5 g/kg) should be estimated using adjusted weight. Systematic use of specific multivitamin supplements is encouraged. Calcium citrate and vitamin D supplements should be used at higher doses than are currently recommended. The use of proton-pump inhibitors should be individualised, and vitamin B12 and iron should be supplemented in case of deficit. All patients, especially pregnant women, teenagers, and elderly patients require a multidisciplinary approach and specialised follow-up. These recommendations and suggestions regarding nutrition management when undergoing bariatric surgery and postoperative follow-up have direct clinical applicability.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD. METHODS: Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison. RESULTS: Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium a

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. METHODS: Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. RESULTS: Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants