Intake of Calcium, Magnesium, and Phosphorus and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

ObjectiveFew epidemiological studies have investigated the associations between calcium, magnesium, and phosphorus intake and pancreatic cancer. We examined these associations in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.MethodsDiet was assessed using the Dietary Questionnaire (DQX) at baseline in the intervention arm and the Dietary History Questionnaire (DHQ) in 1999 or around the third anniversary of randomization in both the intervention and control arms. During a median follow-up of 12.2 years, 279 cases of pancreatic cancer occurred from 58,477 participants who completed DQX; 380 cases arose from 101,622 participants who responded to DHQ over a median follow-up of 8.9 years. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsTotal calcium intake was inversely associated with pancreatic cancer [HR (95% CI) for the fourth vs. the first quartiles in the DHQ cohort: 0.67 (0.47, 0.96); p-trend: 0.035]. An inverse association was also observed for total magnesium intake [HR (95% CI) for the fourth vs. the first quartiles in the DQX cohort: 0.61 (0.37, 1.00); p-trend: 0.023]. Reduced risk associated with total calcium intake was confined to subjects with a high fat intake (>73 g/day) in the DHQ cohort (p-interaction: 0.16).ConclusionsThere was not a significant association between dietary phosphorus intake and pancreatic cancer risk in both cohorts. Total intake of calcium and magnesium are associated with a lower pancreatic cancer risk. The effect of total calcium intake was modified by fat intake.

Magnesium intake was inversely associated with hostility among American young adults.

Hostility is a complex personality trait associated with many cardiovascular risk factor phenotypes. Although magnesium intake has been related to mood and cardio-metabolic disease, its relation with hostility remains unclear. We hypothesize that high total magnesium intake is associated with lower levels of hostility because of its putative antidepressant mechanisms. To test the hypothesis, we prospectively analyzed data in 4,716 young adults aged 18-30 years at baseline (1985-1986) from four U.S. cities over five years of follow-up using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Magnesium intake was estimated from a dietary history questionnaire plus supplements at baseline. Levels of hostility were assessed using the Cook-Medley scale at baseline and year 5 (1990-1991). Generalized estimating equations were applied to estimate the association of magnesium intake with hostility as repeated measures at the two time-points (baseline and year 5). General linear model was used to determine the association between magnesium intake and change in hostility over 5 years. After adjustment for socio-demographic and major lifestyle factors, a significant inverse association was observed between magnesium intake and hostility level over 5 years of follow-up. Beta coefficients (95% CI) across higher quintiles of magnesium intake were 0 (reference), -1.28 (-1.92, -0.65), -1.45 (-2.09, -0.81), -1.41 (-2.08, -0.75) and -2.16 (-2.85, -1.47), respectively (Plinear-trend<.01). The inverse association was independent of socio-demographic and major lifestyle factors, supplement use, and depression status at year 5. This prospective study provides evidence that in young adults, high magnesium intake was inversely associated with hostility level independent of socio-demographic and major lifestyle factors.

Effect of short-term vitamin D supplementation after nonsurgical periodontal treatment: A randomized, double-masked, placebo-controlled clinical trial.

OBJECTIVES: This trial aimed to evaluate the efficacy and safety of vitamin D supplementation on the residual moderate and deep pockets following nonsurgical periodontal therapy. BACKGROUND: Vitamin D supplementation has potential effects on periodontitis, but current evidence remains inconclusive. METHODS: After 3 months of nonsurgical periodontal treatment, 360 patients with moderate or severe periodontitis were randomly assigned to 2000 international unit (IU)/d vitamin D3, 1000 IU/d vitamin D3, or placebo. Clinical periodontal examinations, including probing depth (PD), bleeding index (BI), plaque index (PLI), attachment loss (AL), and alveolar crest height (ACH), were performed at baseline and after 3 months of intervention. RESULTS: There was a slight but significant decrease in AL and PD in both vitamin D groups compared with placebo group for moderate and deep pockets. About 2000 IU/d vitamin D3 group, 1000 IU/d vitamin D3 group, and placebo group all decreased the AL for both moderate pockets (-0.4 mm vs -0.4 mm vs -0.3 mm) and deep pockets (-1.1 mm vs -1.1 mm vs -1.0 mm) (all P < .05). Similarly, PD was also decreased in these three groups for both moderate pockets and deep pockets (all P < .05). In addition, vitamin D supplementation was well tolerated, and no adverse events were reported. CONCLUSIONS: Although statistically significant differences were observed in favor to vitamin D supplementation, the magnitude of effect size tended to be modest with limited clinical relevance and the long-term efficacy and safety warrant further investigation.

Prevalence and trends in dietary supplement use among US adults with diabetes: the National Health and Nutrition Examination Surveys, 1999-2014.

OBJECTIVE: To evaluate overall prevalence and trends of use of any supplements, multivitamins/multiminerals (MVMM), individual vitamins, minerals, and non-vitamin, non-mineral (NVNM) supplements among adults with diabetes in the USA. RESEARCH DESIGN AND METHODS: We used a nationally representative sample from the National Health and Nutrition Examination Survey collected between 1999 and 2014. Information on supplement use in the preceding 30 days was collected during interview over 8 continuous 2-year waves. To account for the complex sampling design, weighted analyses were conducted among 6688 US adults with diabetes aged 20-85 years and also stratified by age, sex, race/ethnicity, education, comorbidity status, and diabetes duration. RESULTS: Overall, the prevalence of any supplement use (52%-58%; P for trend=0.08) and that of any mineral use (47%-51%; P for trend=0.23) seemed stable over the years studied. Reported use of MVMM slightly decreased from 36% to 32% (P for trend=0.006). Use of any vitamin products significantly increased from 47% to 52% (P for trend=0.03). Use of some individual supplements, especially vitamin D, choline, lycopene, and fish oil supplements, significantly increased, while some vitamins, minerals and NVNM supplements decreased over the years. In addition, the trend of any supplement use varied by age, sex, race/ethnicity, or education, but not by diabetes duration or diabetic comorbidities. CONCLUSIONS: Among US patients with diabetes, use of any dietary supplements or any minerals remained stable, while MVMM use slightly decreased and use of any vitamins increased. Additionally, use of several individual supplements varied significantly over the 16-year period studied.

Association of Dietary Magnesium Intake with Fatal Coronary Heart Disease and Sudden Cardiac Death.

Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population.

BACKGROUND & AIMS: The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. METHODS: A total of 2671 participants, aged 40-75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. RESULTS: After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2-4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). CONCLUSIONS: Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.

Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial.

Background: Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium. Objectives: The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration. Methods: The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry. Results: The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased. Conclusion: Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

Longitudinal Maternal Vitamin D Status during Pregnancy Is Associated with Neonatal Anthropometric Measures.

Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother⁻offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies⁻Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10⁻14, 15⁻26, 23⁻31, and 33⁻39 GW and categorized as <50 nmol/L, 50⁻75 nmol/L, and >75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10⁻14 GW, 16.8% and 49.2% of women had 25(OH)D <50 nmol/L and between 50⁻75 nmol/L, respectively. The association of maternal 25(OH)D with neonatal anthropometry differed by GW and women's prepregnancy BMI (normal (<25.0 kg/m²), overweight/obese (25.0⁻44.9 kg/m²)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower birthweight z-score (0.56; 95% CI: -0.99, -0.13) and length (-1.56 cm; 95% CI: -3.07, -0.06), and at 23⁻31 GW was associated with shorter length (-2.77 cm; 95% CI: -13.38, -4.98) and lower sum of skinfolds (-9.18 mm; 95% CI: -13.38, -4.98). Among women with a normal BMI, 25(OH)D <50 nmol/L at 10⁻14 GW was associated with lower sum of skinfolds (-2.64 mm; 95% CI: -5.03, -0.24), at 23⁻31 GW was associated with larger birthweight z-scores (0.64; 95% CI: 0.03, 1.25), and at 33-39 GW with both higher birthweight z-score (1.22; 95% CI: 0.71, 1.73) and longer length (1.94 cm; 95% CI: 0.37, 3.52). Maternal 25(OH)D status during pregnancy was associated with neonatal anthropometric measures, and the associations were specific to GW of 25(OH)D measurement and prepregnancy BMI.

Effects of Vitamin D Supplementation on Glucose and Insulin Homeostasis and Incident Diabetes among Nondiabetic Adults: A Meta-Analysis of Randomized Controlled Trials.

AIMS: Emerging evidence has suggested a mechanistic link from vitamin D metabolism to glucose and insulin homeostasis. This study is aimed at specifically quantifying the direct effects of vitamin D supplementation on indexes of glucose and insulin homeostasis as well as incidence of type 2 diabetes (T2D) among nondiabetic adults. METHODS: We systematically searched randomized controlled trials (RCTs) of vitamin D supplementation in nondiabetic adults in PubMed, EMBASE, and CENTRAL. Random-effects meta-analysis was conducted to pool the estimates. RESULTS: Our meta-analysis included 47 RCTs involving 44,161 nondiabetic individuals with a median trial duration of 4 months and a median dose of 4000 IU/d. Vitamin D supplementation significantly reduced fasting glucose by 0.11 mmol/L, fasting insulin by 1.47 mIU/L, and HOMA-IR by 0.32 while increasing total 25 (OH) D levels by 40.14 nmol/L. We found no significant effects of vitamin D supplementation on insulin secretion or beta cell function indexes. Based on the data from six trials involving 39,633 participants and 2533 incident T2D cases, vitamin D supplementation was not associated with the risk of incident diabetes compared to placebo (pooled relative risk: 1.01, 95% confidence interval: 0.93 to 1.08). CONCLUSIONS: Our meta-analysis found that vitamin D supplementation might improve glucose and insulin metabolism without affecting the risk of T2D among nondiabetic adults.

Prepregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the effect of vitamin D intake, either from the diet or from supplements, on the development of gestational diabetes mellitus (GDM) remains unclear. We prospectively examined the association of prepregnancy habitual intake of vitamin D from diet and supplements with the risk of incident GDM in a well-established cohort. METHODS: The present study was performed on 21 356 singleton pregnancies from 15 225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intake from food sources and supplements, was assessed in 1991 and every 4 years thereafter by validated food frequency questionnaires. Log-binomial models with generalized estimating equations were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 10 years of follow-up, 865 incident GDM cases were documented. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1-399, and ≥400 IU/day were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (Ptrend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. CONCLUSIONS: Prepregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.

The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials.

Background: To our knowledge, the effect of magnesium supplementation on blood pressure (BP) in individuals with preclinical or noncommunicable diseases has not been previously investigated in a meta-analysis, and the findings from randomized controlled trials (RCTs) have been inconsistent.Objective: We sought to determine the pooled effect of magnesium supplementation on BP in participants with preclinical or noncommunicable diseases.Design: We identified RCTs that were published in English before May 2017 that examined the effect of magnesium supplementation on BP in individuals with preclinical or noncommunicable diseases through PubMed, ScienceDirect, Cochrane, clinicaltrials.gov, SpringerLink, and Google Scholar databases as well as the reference lists from identified relevant articles. Random- and fixed-effects models were used to estimate the pooled standardized mean differences (SMDs) with 95% CIs in changes in BP from baseline to the end of the trial in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the magnesium-supplementation group and the control group.Results: Eleven RCTs that included 543 participants with follow-up periods that ranged from 1 to 6 mo (mean: 3.6 mo) were included in this meta-analysis. The dose of elemental magnesium that was used in the trials ranged from 365 to 450 mg/d. All studies reported BP at baseline and the end of the trial. The weighted overall effects indicated that the magnesium-supplementation group had a significantly greater reduction in both SBP (SMD: -0.20; 95% CI: -0.37, -0.03) and DBP (SMD: -0.27; 95% CI: -0.52, -0.03) than did the control group. Magnesium supplementation resulted in a mean reduction of 4.18 mm Hg in SBP and 2.27 mm Hg in DBP.Conclusion: The pooled results suggest that magnesium supplementation significantly lowers BP in individuals with insulin resistance, prediabetes, or other noncommunicable chronic diseases.

Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials.

The antihypertensive effect of magnesium (Mg) supplementation remains controversial. We aimed to quantify the effect of oral Mg supplementation on blood pressure (BP) by synthesizing available evidence from randomized, double-blind, placebo-controlled trials. We searched trials of Mg supplementation on normotensive and hypertensive adults published up to February 1, 2016 from MEDLINE and EMBASE databases; 34 trials involving 2028 participants were eligible for this meta-analysis. Weighted mean differences of changes in BP and serum Mg were calculated by random-effects meta-analysis. Mg supplementation at a median dose of 368 mg/d for a median duration of 3 months significantly reduced systolic BP by 2.00 mm Hg (95% confidence interval, 0.43-3.58) and diastolic BP by 1.78 mm Hg (95% confidence interval, 0.73-2.82); these reductions were accompanied by 0.05 mmol/L (95% confidence interval, 0.03, 0.07) elevation of serum Mg compared with placebo. Using a restricted cubic spline curve, we found that Mg supplementation with a dose of 300 mg/d or duration of 1 month is sufficient to elevate serum Mg and reduce BP; and serum Mg was negatively associated with diastolic BP but not systolic BP (all P<0.05). In the stratified analyses, a greater reduction in BP tended to be found in trials with high quality or low dropout rate (all P values for interaction <0.05). However, residual heterogeneity may still exist after considering these possible factors. Our findings indicate a causal effect of Mg supplementation on lowering BPs in adults. Further well-designed trials are warranted to validate the BP-lowering efficacy of optimal Mg treatment.

The Circulating Concentration and 24-h Urine Excretion of Magnesium Dose- and Time-Dependently Respond to Oral Magnesium Supplementation in a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification. OBJECTIVE: We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs). METHODS: We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation. RESULTS: Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity ≤ 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses. CONCLUSIONS: This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.

Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.

Effect of vitamin D supplementation alone or with calcium on adiposity measures: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: The independent or interactive effects of vitamin D and calcium on adiposity remain inconclusive. OBJECTIVE: The objective of this systematic review and meta-analysis was to assess whether vitamin D and calcium supplements cause changes in adiposity. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for literature published from 1966 to March 2014. STUDY SELECTION: A systematic search was conducted for randomized clinical trials with ≥ 50 participants aged ≥ 18 years at baseline who had received at least 12 weeks of treatment. Among the inclusion criteria were supplementation with vitamin D with or without calcium and measurement of adiposity (weight, body mass index [BMI], and/or fat mass). DATA EXTRACTION: The primary endpoints assessed were changes in weight, BMI, or fat mass. DATA SYNTHESIS: Of 953 trials identified, 26 randomized clinical trials (n = 12, vitamin D alone; n = 10, vitamin D plus calcium versus calcium control; n = 4, vitamin D plus calcium versus placebo) with a total of 42,430 participants (median duration, 12 months) met the inclusion criteria. When compared with placebo, vitamin D supplementation had no significant effect on BMI (weighted mean difference [WMD], -0.06 kg/m(2); 95% confidence interval [95%CI], -0.14 to 0.03), weight (WMD, -0.05 kg; 95%CI, -0.32 to 0.23), or fat mass (WMD, -0.43 kg; 95%CI, -1.69 to 0.84). Likewise, no significant reduction in BMI (WMD, 0.02 kg/m(2); 95%CI, -0.11 to 0.14), weight (WMD, 0.12 kg; 95%CI, -0.24 to 0.49), or fat mass (WMD, 0.12 kg; 95%CI, -0.22 to 0.45) was observed in participants who received vitamin D plus calcium compared with those who received calcium control. CONCLUSIONS: Supplementation with vitamin D showed no effect on adiposity measures in adults.

Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and Hispanic American women.

BACKGROUND: Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. OBJECTIVE: We examined the association of common genetic variants [single nucleotide polymorphisms (SNPs)] in genes related to magnesium homeostasis with T2D risk and potential interactions with magnesium intake. METHODS: Using the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe) study, we identified 17 magnesium-related ion channel genes (583 SNPs) and examined their associations with T2D risk in 7287 African-American (AA; n = 1949 T2D cases) and 3285 Hispanic-American (HA; n = 611 T2D cases) postmenopausal women. We performed both single- and multiple-locus haplotype analyses. RESULTS: Among AA women, carriers of each additional copy of SNP rs6584273 in cyclin mediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P = 0.02]. Among HA women, several variants were significantly associated with T2D risk, including rs10861279 in solute carrier family 41 (anion exchanger), member 2 (SLC41A2) (OR: 0.54; FDR-adjusted P = 0.04), rs7174119 in nonimprinted in Prader-Willi/Angelman syndrome 1 (NIPA1) (OR: 1.27; FDR-adjusted P = 0.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR = 1.48, FDR-adjusted P = 0.02). Even with the most conservative Bonferroni adjustment, two 2-SNP-haplotypes in SLC41A2 and MRS2 region were significantly associated with T2D risk (rs12582312-rs10861279: P = 0.0006; rs1056285-rs7738943: P = 0.002). Among women with magnesium intake in the lowest 30% (AA: ≤0.164 g/d; HA: ≤0.185 g/d), 4 SNP signals were strengthened [rs11590362 in claudin 19 (CLDN19), rs823154 in SLC41A1, rs5929706 and rs5930817 in membra; HA: ≥0.313 g/d), rs6584273 in CNNM1 (OR: 0.71; FDR-adjusted P = 0.04) and rs1800467 in potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) (OR: 2.50; FDR-adjusted P = 0.01) were significantly associated with T2D risk. CONCLUSIONS: Our findings suggest important associations between genetic variations in magnesium-related ion channel genes and T2D risk in AA and HA women that vary by amount of magnesium intake.

Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative.

BACKGROUND: Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF. METHODS AND RESULTS: Analyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups. CONCLUSIONS: CaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Vitamin D levels and menopause-related symptoms.

OBJECTIVE: This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women. METHODS: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses. RESULTS: Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10 for fully adjusted models). CONCLUSIONS: There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

OBJECTIVE: The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. METHODS: The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women's Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. RESULTS: There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46-mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). CONCLUSIONS: Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.