High Calcium Intake Research Articles

Calcium supplementation and cardiovascular risk: A rising concern.

Over the past decade, the number of individuals taking calcium supplementation worldwide has been on the rise, especially with the emergence of new pharmaceutical companies specialized in the marketing of dietary supplements; with calcium supplementation being their main business axis. This is mostly because of the established role of calcium in the prevention and treatment of osteoporosis and, to a lesser extent, its role in the prevention of fractures. Recently, a rising body of evidence on the adverse effect of calcium supplementation on nonskeletal, especially cardiovascular, health has been a cause for concern. In fact, a significant number of studies have reported an association between calcium supplementation and adverse cardiovascular events, even though high dietary calcium intake was shown to have a protective effect. The mechanism by which calcium supplementation could cause a cardiovascular event was still unclear until a recent study published in the Journal of the American Heart Association. Combining this recent finding with available data associating calcium supplementation with cardiovascular mortality and all-cause mortality, we call on the need for an evidence-based approach to calcium supplementation, while stressing on the safety of dietary calcium intake over the former on cardiovascular health.

Consumption of fortified infant foods reduces dietary diversity but has a positive effect on subsequent growth in infants from Sumedang district, Indonesia.

Stunting and underweight among under-five children in Indonesia are common, raising public health concerns. Whether inappropriate complementary feeding (CF) practices compromise optimal growth during late infancy in Indonesia is uncertain. Therefore we characterized and evaluated CF practices in Indonesian infants and investigated their relationship with subsequent growth. We enrolled breastfed infants at 6 months of age (n = 230); and followed them at 9 (n = 202) and 12 months of age (n = 190). We collected socio-demographic and anthropometric data and two-day in-home weighed food records. Relations between WHO CF indicators, sentinel foods, and energy and micronutrient intakes at 9 months and growth at 12 months were explored using multiple linear regression. Stunting and underweight increased from 15.8% and 4.4% at 6 months to 22.6% and 10.5% at 12 months, respectively. Median intakes of calcium, iron, zinc, and riboflavin were below WHO recommendations. Infants consuming fortified infant foods (FIFs) at 9 months had diets with a lower dietary diversity (DD) score (2.3 vs.3.0), energy density, median energy (250 vs. 310 kcal/d) and protein (6.5 vs. 9.1 g/d) intake than non-consumers (p<0.01), despite higher intakes of calcium, iron, and vitamins A and C (p<0.001). Positive relations existed for 9-month consumption of iron-rich/iron fortified infant foods with length-for-age Z-score (LAZ) at 12 months (β = 0.22; 95% CI: 0.01, 0.44; P = 0.04), and for fortified infant foods alone with both LAZ (β = 0.29; 95% CI: 0.09, 0.48; P = 0.04) and weight-for-age Z-score (β = 0.14; 95% CI: 0.02, 0.26; P = 0.02) at 12 months. The positive association of FIFs with subsequent growth may be attributed to their content of both powdered cow’s milk and multi-micronutrient fortificants. Nonetheless, mothers should not be encouraged to over-rely on FIFs as they reduce DD.

Nutrient patterns and risk of cataract: a case-control study.

To assess the relation between nutrient patterns and cataract risk. This is a hospital-based case-control study with 97 cataract patients and 198 matched controls. Dietary consumption was collected through a valid food frequency questionnaire (FFQ). Nutrient patterns were detected by applying factor analysis. Unconditional logistic regression models were used to estimate odds ratio (ORs) and 95%CIs. We extracted 5 main nutrient patterns. Factor 1 included niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium (sodium pattern). Factor 2 was characterized by oleic acid, monounsaturated fats, polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E and saturated fats (fatty acid pattern). The third factor represented high intake of vitamin B12, vitamin D, cholesterol and calcium (mixed pattern). The 4th pattern was high in intake of beta and alpha carotene, vitamin A and vitamin C (antioxidant pattern). Finally, the 5th pattern loaded heavily on docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (omega-3 pattern). In crude and multivariate analysis, the sodium pattern was associated with increased risk of cataract (OR=1.97, 95%CI: 1.09-3.96). The fatty acid pattern elevated the risk of cataract (OR=1.94, 95%CI: 1.1-3.86). Antioxidant pattern was associated with a significant 79% reduced risk (2nd category compared with the 1st). Omega-3 pattern was significantly negatively associated with risk of cataract (P=0.04). These findings imply that nutrient patterns reflecting a combined consumption of nutrients might be important in the etiology of cataract. Additional studies with more efficient designs are warranted to confirm our findings.

Impact of air pollution on vitamin D deficiency and bone health in adolescents.

The aim of this study was to evaluate the association between ambient air pollution and bone turnover in adolescents and to compare the prevalence of vitamin D deficiency between polluted and non-polluted areas of Tehran. This cross-sectional population-based study was conducted on 325 middle- and high-school students (both girls and boys) in Tehran in the winter. During the study period, detailed daily data on air pollution were obtained from archived data collected by Tehran Air Quality Control Company (AQCC). Serum levels of calcium, phosphorus, parathyroid hormone (PTH), bone-specific alkaline phosphatase, 25(OH) vitamin D, osteocalcin, cross-linked C-telopeptide (CTX), total protein, albumin, and creatinine were obtained from the study group. Vitamin D deficiency was more prevalent in polluted areas than in non-polluted areas. After adjustment for age and sex, residence in the polluted area showed a statistically significant positive association with vitamin D deficiency and a statistically significant negative association with bone turnover. Interestingly, high calcium intake (>5000mg/week) protects against the effects of air pollution on bone turnover. Air pollution is a chief factor determining the amount of solar UVB that reaches the earth's surface. Thus, atmospheric pollution may play a significant independent role in the development of vitamin D deficiency.

High Vitamin D Intake Improves Bone Health in Obesity

The impact of obesity on bone health remains controversial. Obesity is often considered “beneficial” to bone health because high body weight imposes a large mechanical load on weight‐bearing bones leading to increased bone mass and strength to accommodate such a load. The mechanical implications and hormonal effects of obesity on the growing, forming bone can be different from those effects on the mature bone. The active form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) is the hormonal regulator of bone formation, mineralization and remodeling, and low vitamin D status is routinely observed in obesity. We hypothesized that (1) an increased body weight is detrimental to the growing bone due to its high rate of formation and low level of mineralization and that (2) regulation of bone mineral (Ca and P) and matrix (collagen) status via the vitamin D endocrine system is impaired in obesity because of secondary vitamin D insufficiency. The aim of this study was to examine the effects of the increased vitamin D3 intake, alone and in combination with increased calcium intake, on the bone status in a diet‐induced obesity (DIO) mouse model. Male mice were fed for 10 weeks a high‐fat diet (DIO) containing high levels of vitamin D3 (10,000 IU/kg vs. 1,000 IU/kg in control), calcium (1.2% vs. 0.55% in control), or vitamin D3 plus calcium (10,000 IU/kg D3 plus 1.2% Ca vs. 1,000 IU/kg D3 plus 0.55% Ca). Bone weight, specific gravity, mineral (Ca and P) and collagen (hydroxyproline) content were measured in the femur and the tibia. Regulators of Ca2+ metabolism and markers of bone status (parathyroid hormone (PTH), 25‐hydroxyvitamin D (25(OH)D), 1,25(OH)2D3, and osteocalcin) were measured in blood plasma. DIO mice had a lower bone mineral (Ca and P) content and relative bone weight compared to the normal control; the collagen content was not changed. DIO was accompanied by a decrease in 25(OH)D and 1,25(OH)2D3 concentrations, whereas PTH and osteocalcin concentrations were increased. High vitamin D3 and calcium intakes significantly increased bone Ca and P content and relative bone weight in DIO mice, which was accompanied by an increase in 1,25(OH)2D3 concentration and a decrease in PTH and osteocalcin concentrations in blood. DIO mice were characterized by obese phenotype, elevated blood glucose and impaired glucose tolerance, increased insulin and decreased adiponectin concentrations in blood, and a decreased level of adipocyte apoptosis in adipose tissue. DIO mice fed diet with high vitamin D3 and increased calcium content demonstrated significantly improved blood markers related to vitamin D status and adiposity as well as a decreased weight of white adipose tissue depots due to increased level of adipocyte apoptosis. The major results of the present study indicate that high vitamin D and calcium intake is effective in increasing mineral content in the growing bone of obese mice and that the hormonal mechanism of this effect involves the vitamin D – PTH axis. The findings obtained strongly imply that increasing vitamin D and calcium intakes may contribute to prevention of “obesity” of bone and obesity‐related causes contributing to obese bone (diabetes mellitus, secondary hyperparathyroidism and vitamin D insufficiency).Support or Funding InformationSupported by USDA SD00H533.

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

BackgroundAfrican Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples.MethodsA total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables.ResultsIn the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 1.98, 95% C.I.: 1.01–3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 0.38, 95% C.I.: 0.18–0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70–10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02–0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m2), but not among men with high BMI (≥27.8 kg/m2). Interactions of race and BMI with vitamin D intake were significant (PInteraction < 0.05).ConclusionCalcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.

Plant-based diets relatively low in bioavailable phosphate and calcium may aid prevention and control of prostate cancer by lessening production of fibroblast growth factor 23

Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases. Hence, dietary or lifestyle factors which boost bone’s production of FGF23 may encourage the induction and spread of prostate cancer. High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer. Hence, prospective studies correlating baseline FGF23 levels with subsequent risk for prostate cancer, or advanced prostate cancer, are needed. Natural plant-based diets, though not inherently low in calcium or phosphorus, provide forms of these that are less bioavailable than those in animal products, and hence may be expected to down-regulate bone’s production of FGF23. This may play a role in the lower risk for clinical prostate cancer observed in vegans and quasi-vegan cultures. Other factors, such as decreased IGF-I levels and mTORC1 activity, may also play a role in this regard.

Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10-Year Follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA).

BackgroundRecent 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 ResultsWe 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.ConclusionsHigh 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.

Effects of Different Levels of Calcium Intake on Brain Cell Apoptosis in Fluorosis Rat Offspring and Its Molecular Mechanism.

The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

Certain subsets of colorectal serrated polyps (SP) have malignant potential. We performed a systematic review and meta-analysis to investigate the association between modifiable lifestyle factors and risk for SPs. We conducted a systematic search of Medline, Embase, and Web of Science for observational or interventional studies that contained the terms risk or risk factor, and serrated or hyperplastic, and polyps or adenomas, and colorectal (or synonymous terms), published by March 2016. Titles and abstracts of identified articles were independently reviewed by at least 2 reviewers. Adjusted relative risk (RR) and 95% confidence interval (CI) were combined using random effects meta-analyses to assess the risk of SP, when possible. We identified 43 studies of SP risk associated with 7 different lifestyle factors: smoking, alcohol, body fatness, diet, physical activity, medication, and hormone-replacement therapy. When we compared the highest and lowest categories of exposure, factors we found to significantly increase risk for SP included tobacco smoking (RR, 2.47; 95% CI, 2.12-2.87), alcohol intake (RR, 1.33; 95% CI, 1.17-1.52), body mass index (RR, 1.40; 95% CI, 1.22-1.61), and high intake of fat or meat. Direct associations for smoking and alcohol, but not body fat, tended to be stronger for sessile serrated adenomas/polyps than hyperplastic polyps. In contrast, factors we found to significantly decrease risks for SP included use of nonsteroidal anti-inflammatory drugs (RR, 0.77; 95% CI, 0.65-0.92) or aspirin (RR, 0.81; 95% CI, 0.67-0.99), as well as high intake of folate, calcium, or fiber. No significant associations weredetected between SP risk and physical activity or hormone replacement therapy. Several lifestyle factors, most notably smoking and alcohol, are associated with SP risk. These findings enhance our understanding of mechanisms of SP development and indicate that risk of serrated pathway colorectal neoplasms could be reduced with lifestyle changes.

Calcium intake and colorectal cancer risk: Results from the nurses' health study and health professionals follow-up study.

The relationship between calcium intake and colorectal cancer (CRC) risk remains inconclusive. We conducted this study to evaluate whether the association between calcium intake and CRC risk differs by anatomic subsite and determine the dose-response relationship for this association, as well as assess when in carcinogenesis calcium may play a role. We assessed calcium intake every 4 years and followed 88,509 women (1980-2012) in the Nurses' Health Study and 47,740 men (1986-2012) in the Health Professionals Follow-Up Study. We documented 3,078 incident CRC cases. Total calcium intake (≥1,400 vs. <600 mg/d) was associated with a statistically significant lower risk of colon cancer (multivariable relative risk: 0.78, 95%CI: 0.65-0.95). Similar results were observed by different sources of calcium (from all foods or dairy products only). The inverse association was linear and suggestively stronger for distal colon cancer (0.65, 0.43-0.99) than for proximal colon cancer (0.94, 0.72-1.22, p-common effects = 0.14). Additionally, when comparing different latencies, the overall pattern suggested that the inverse association appeared to be stronger with increasing latency and was strongest for intakes 12-16 years before diagnosis. Comparing total calcium intakes of ≥1,400 vs. <600 mg/d for intake 12-16 y before diagnosis, the pooled RR (95% CIs) of CRC was 0.76 (0.64-0.91). Higher calcium intake was associated with a lower risk of developing colon cancer, especially for distal colon cancer. Overall inverse association was linear and did not differ by intake source. Additionally, calcium intake approximately 10 years before diagnosis appeared to be associated with a lower risk of CRC.

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease

Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched dietalone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.

Abstract 1739: Calcium to magnesium intake ratio and colorectal carcinogenesis, results from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial

Abstract Background A recent randomized trial found no effect of calcium supplementation on reducing risk of colorectal adenoma recurrence. However, the role of calcium in carcinogenesis is yet unconfirmed. An earlier trial found calcium treatment only reduced recurrence when the baseline calcium: magnesium intake ratio was &amp;lt;2.6. Nor is it clear whether calcium intake is differentially related to risks of different stages of colorectal carcinogenesis (incident adenoma, adenoma recurrence and incident colorectal cancer). Further, it is unclear if calcium intake or supplementation confers additional protection against incident colorectal cancer in individuals receiving endoscopic screenings. To address these important scientific inquiries, we have conducted analyses within the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods The PLCO is a large, multicenter, population-based randomized trial designed to determine the effects of screening on cancer-related mortality with a median of 12.5 years of follow up. We evaluated the associations between calcium intake and the risks of incident colorectal adenoma (1,147 cases), recurrent adenoma (855 cases) and incident colorectal cancer (697 and 578 cases in intervention and control arms, respectively) among 108,563 PLCO participants aged 55 to 74 years. Odds ratios (OR) and 95% confidence intervals (95%CIs) for incident adenoma and recurrent adenoma, and hazard ratios (HR) and 95%CIs for colorectal cancer incidence were calculated using unconditional logistic regression models and Cox proportional hazard models after adjusting covariates. Results Compared to low calcium intake (&amp;lt;600 mg/day), higher intakes of calcium were not related to a reduced risk of incidence adenoma, but significantly associated with a reduced risk of advanced/multiple adenomas (p for trend, &amp;lt;0.05). Further, the significant inverse association only appeared when calcium:magnesiuim intake ratios between 1.7 and 2.5. No significant association was observed between Ca intake and risk of adenoma recurrence. In the control arm, we found, compared to low calcium intake, higher intakes of calcium were associated with significantly reduced risks of incident colorectal cancer, primarily distal cancer. Again, we found the inverse association may primarily appear in those with calcium:magnesiuim intake ratios between 1.7 and 2.5. In contrast, in the intervention arm (i.e. screening with flexible sigmoidoscopy), overall, we did not find any significant associations. Conclusion Intake of calcium may be more strongly related to reduced risks of incident advanced/multiple adenoma and incident colorectal cancer among those without active screening with flexible sigmoidoscopy than to recurrent adenoma and incident colorectal cancer risks among those with active screening with flexible sigmoidoscopy. Citation Format: Jing Zhao, Xiangzhu Zhu, Martha J. Shrubsole, Todd L. Edwards, Edward L. Giovannucci, Wei Zheng, Qi Dai, PLCO Project Team. Calcium to magnesium intake ratio and colorectal carcinogenesis, results from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1739.

Influence of dietary calcium intake on quantitative and qualitative parameters of bone tissue in Polish adults.

The objective of the study was to assess dietary calcium intake in the Polish population and its influence on selected parameters of bone tissue. 1,129 osteoporosis treatment-naive subjects, aged 20-80 years, randomly selected, were involved in the study. Bone status was established using densitometry of spine and hip and quantitative ultrasound of the calcaneus. Dietary calcium intake was calculated according to data gathered in a questionnaire. Median calcium intake was 746 mg; 72% of subjects had calcium intake below the recommended dose. Calcium intake correlated negatively with age (r = -0.15; p<0.001) and positively with BMD in the spine (r = 0.06; p<0.05) and in the femoral neck (r = 0.07; p < 0.05). In subjects with the lowest calcium intake, a significantly lower femoral neck BMD and heel stiffness was noticed than in subjects with the highest calcium intake. However, multiple regression analysis showed that dietary calcium was not a predictor of low BMD, both in the hip and spine, as well as of bone stiffness in contrast to age, low BMI and female gender (p<0.0001). In all factors regression analysis, a weak influence of calcium intake on BMD was shown only in the subgroup of premenopausal women (β = 0.1; p<0.05). In most subjects, dietary calcium intake was below the recommended dose; however, its influence on bone seems to be weak, except for persons with the greatest deficiency of dietary calcium and the subgroup of premenopausal women.

Calcium and 1,25-dihydroxyvitamin D3 modulate genes of immune and inflammatory pathways in the human colon: a human crossover trial1–3

A high dietary calcium intake with adequate vitamin D status has been linked to lower colorectal cancer risk, but the mechanisms of these effects are poorly understood. The objective of this study was to elucidate the effects of a Western-style diet (WD) and supplemental calcium and/or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the colorectal mucosa. We conducted 2 crossover trials to define molecular pathways in the human colorectum altered by 1) a 4-wk WD supplemented with and without 2 g calcium carbonate/d and 2) a 4-wk WD supplemented with 1,25(OH)2D3 (0.5 μg/d) with or without 2 g calcium carbonate/d. The primary study endpoint was genome-wide gene expression in biopsy specimens of the rectosigmoid colonic mucosa. Serum and urinary calcium concentrations were also measured. Changes in urinary calcium accurately reflected calcium consumption. The WD induced modest upregulation of genes involved in inflammatory pathways, including interferon signaling, and calcium supplementation reversed these toward baseline. In contrast, supplementation of the WD with 1,25(OH)2D3 induced striking upregulation of genes involved in inflammation, immune response, extracellular matrix, and cell adhesion. Calcium supplementation largely abrogated these changes. Supplementing 1,25(OH)2D3 to a WD markedly upregulated genes in immune response and inflammation pathways, which were largely reversed by calcium supplementation. This study provides clinical trial evidence of global gene expression changes occurring in the human colorectum in response to calcium and 1,25(OH)2D3 intervention. One action of 1,25(OH)2D3 is to upregulate adaptive immunity. Calcium appears to modulate this effect, pointing to its biological interaction in the mucosa. This trial was registered at clinicaltrials.gov as NCT00298545 Trial protocol is available at http://clinicalstudies.rucares.org (protocol numbers PHO475 and PHO554).

Is vaccenic acid (18:1t n-7) associated with an increased incidence of hip fracture? An explanation for the calcium paradox

High calcium intake may increase hip fracture (HF) incidence. This phenomenon, known as the calcium paradox, might be explained by vaccenic acid (18:1t n-7, VA), the highly specific trans fatty acid (TFA) present in dairy products. First, we ecologically investigated the relationship between 18:1 TFA intake and HF incidence using data from 12 to 13 European countries collected before 2000; then we measured the effects of VA and elaidic acid (18:1t n-9, EA) on osteoblasts from goldfish scales (tissues very similar to mammalian bone), with alkaline phosphatase as a marker; and finally we measured the effect of VA on mRNA expression in the scales for the major bone proteins type I collagen and osteocalcin. HF incidence was significantly correlated with 18:1 TFA intake in men (r=0.57) and women (r=0.65). Incubation with 1μmol/L VA and EA for 48h significantly decreased alkaline phosphatase activity by 25% and 21%, respectively. Incubation of scales with 10μmol/L VA for 48h significantly decreased mRNA expression for type I collagen and osteocalcin (by about 50%). In conclusion, VA may be causatively related to HF and could explain the calcium paradox. It may be prudent to reduce 18:1 TFA intake, irrespective of trans positions, to prevent HF.

Serum 25-hydroxyvitamin D and metabolic syndrome in a Japanese working population: The Furukawa Nutrition and Health Study

ObjectiveIncreasing evidence has suggested a protective role of vitamin D on metabolic syndrome (MetS). However, studies addressing this issue are limited in Asia and it remains unclear whether calcium could modify the association. We examined the association of serum 25-hydroxyvitamin D (25(OH)D) status with MetS, and the potential effect modification by calcium intake in a Japanese working population. MethodsStudy subjects were 1790 workers, ages 18 to 69 y, who participated in a health survey at the time of periodic checkup. MetS was defined according to the joint interim statement. Serum 25(OH)D was measured by a protein binding assay. Multilevel logistic regression was used to estimate the odds ratio (OR) with adjustment for potential confounding variables. ResultsAn inverse trend was observed between 25(OH)D and MetS. Compared with those with a 25(OH)D of <20 ng/mL, multivariable adjusted OR (95% confidence interval) for MetS was 0.79 (0.55–1.15) and 0.52 (0.25–1.04) for those with a 25(OH)D of 20 to 29 ng/mL and ≥30 ng/mL, respectively (P for trend = 0.051). Similar association was observed in the analysis using quartile categories of 25(OH)D; the OR in the highest quartile of 25(OH)D compared with the lowest quartile was 0.61 (0.36–1.01) (P for trend = 0.046). This association was noted only in older subjects (≥44 y). The inverse association between serum 25(OH)D and MetS was more pronounced in subjects with high calcium intake. The inverse association between 25(OH)D and MetS appears to be linear according to restricted cubic spline regression. There was inverse, but statistically nonsignificant, associations between 25(OH)D and each component of MetS. ConclusionOur results suggest that higher circulating vitamin D is associated with decreased likelihood of having MetS among Japanese adults.

Physical Activity and the Risk of Primary Hyperparathyroidism.

Primary hyperparathyroidism (P-HPTH) is relatively common and predominantly affects women. Prior studies have shown that physical activity (PA) can lower PTH levels. Our objective was to evaluate the hypothesis that lower PA is a risk factor for developing P-HPTH. This prospective cohort study included 69 621 female participants in the Nurses' Health Study I followed for 22 years. PA and other dietary and demographic exposures were quantified via detailed, and validated, biennial questionnaires. Incident P-HPTH was confirmed by medical record review after initial assessment by questionnaire. Adjusted Cox proportional hazards models were used to evaluate whether PA was an independent risk factor for developing P-HPTH. We also evaluated the risk of developing P-HPTH when combining low PA (<16 metabolic equivalent hours/week) with a previously identified independent risk factor for developing P-HPTH: low calcium intake (<800 mg/day). The relation between PA and PTH levels was evaluated in 625 participants. We confirmed 302 incident cases of P-HPTH during 1 474 993 person-years of follow-up. Participants in the highest quintile (Q) of PA had a 50% lower risk of developing P-HPTH: age-adjusted relative risks and 95% confidence intervals for incident P-HPTH by lowest to highest of PA were Q1 = 1.0 (reference); Q2 = 0.83 (0.60–1.15); Q3 = 0.84 (0.61–1.15); Q4 = 0.50 (0.34–0.74); Q5 = 0.50 (0.35–0.73); P for trend <.001. Extensive multivariable adjustments did not materially change these findings. The adjusted relative risk for developing P-HPTH among participants with the combination lower PA and lower calcium intake was 2.37-fold (1.60–3.51) higher than in participants with higher PA and higher calcium intake. PA was inversely correlated with serum PTH (ρ = −0.09, P = .03); the mean adjusted serum PTH in Q 2–5 of PA was lower than in Q 1 (36.3 vs 39.1 pg/mL, P = .02). Low physical activity may be a modifiable risk factor for developing P-HPTH in women.

Segment-specific Ca2+ transport by isolated Malpighian tubules of Drosophila melanogaster: A comparison of larval and adult stages

Haemolymph calcium homeostasis in insects is achieved through the regulation of calcium excretion by Malpighian tubules in two ways: (1) sequestration of calcium within biomineralized granules and (2) secretion of calcium in soluble form within the primary urine. Using the scanning ion-selective electrode technique (SIET), basolateral Ca2+ transport was measured at the distal, transitional, main and proximal tubular segments of anterior tubules isolated from both 3rd instar larvae and adults of the fruit fly Drosophila melanogaster. Basolateral Ca2+ transport exceeded transepithelial secretion by 800-fold and 11-fold in anterior tubules of larvae and adults, respectively. The magnitude of Ca2+ fluxes across the distal tubule of larvae and adults were larger than fluxes across the downstream segments by 10 and 40 times, respectively, indicating a dominant role for the distal segment in whole animal Ca2+ regulation. Basolateral Ca2+ transport across distal tubules of Drosophila varied throughout the life cycle; Ca2+ was released by distal tubules of larvae, taken up by distal tubules of young adults and was released once again by tubules of adults ⩾168h post-eclosion. In adults and larvae, SIET measurements revealed sites of both Ca2+ uptake and Ca2+ release across the basolateral surface of the distal segment of the same tubule, indicating that Ca2+ transport is bidirectional. Ca2+ uptake across the distal segment of tubules of young adults and Ca2+ release across the distal segment of tubules of older adults was also suggestive of reversible Ca2+ storage. Our results suggest that the distal tubules of D. melanogaster are dynamic calcium stores which allow efficient haemolymph calcium regulation through active Ca2+ sequestration during periods of high dietary calcium intake and passive Ca2+ release during periods of calcium deficiency.

High dietary calcium intake and a lack of dairy consumption are associated with metabolic syndrome in obese males: the Korean National Health and Nutrition Examination Survey 2010 to 2012

Metabolic syndrome (MetS) has been increasing rapidly worldwide and is associated with elevated risks of cardiovascular disease and mortality. The relationship between MetS and dietary calcium intake is controversial. We hypothesized that high dietary calcium intake is associated with MetS in males and that the associations vary according to obesity status. Using data from the Korean National Health and Nutrition Examination Survey V, a cross-sectional survey of Korean civilians was conducted from January 2010 to December 2012 to test these hypotheses. Data from a total of 5946 males were analyzed with no association observed between dietary calcium intake and the presence of MetS. However, males deriving high calcium intake levels from dairy products had a lower prevalence of MetS than did those who did not ingest such products (adjusted odds ratio [OR], 0.75; 95% confidence interval [CI], 0.58-0.96). In obese males, the highest dietary calcium intake was positively associated with the presence of MetS (adjusted OR, 1.61; 95% CI, 1.12-2.36). However, obese males who consume dairy products had a lower prevalence of MetS than did those who did not consume such products (adjusted OR, 0.51; 95% CI, 0.29-0.90). In conclusion, the results suggest that the high dietary calcium intake, in the absence of dairy product consumption, was associated with the increased prevalence of MetS in obese males. Additional studies are required to determine whether dietary calcium intake affects the development of MetS.