Higher Magnesium Intake Research Articles

Magnesium intake, bone mineral density, and fractures: results from the Women’s Health Initiative Observational Study

Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear. We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD). This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants. Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001]. Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls.

Abstract P223: Dietary Magnesium and the Risk of Stroke among Women

Background: Epidemiology studies suggest that high magnesium intake may decrease the risk of stroke by reducing hypertension, endothelial dysfunction and carotid artery thickness, but the results are inconsistent. We therefore examined the association between magnesium intake and stroke type in a cohort with repeated measurement of diet, long duration of follow up, and a large sample size. Methods: We prospectively followed 86,149 women in the Nurses’ Health Study, aged 35 to 55 years, who were free of diagnosed cardiovascular disease and cancer at baseline in 1980. Data on dietary intake were collected with a semi-quantitative food frequency questionnaire at baseline in 1980, 1984, 1986 and then every 4 years, while data on stroke, stroke risk factors and potential confounders were collected at baseline and updated biennially. Strokes were classified according to the National Survey of Stroke criteria; and strokes for which medical records were not available were classified as probable/unknown. We calculated the hazard ratio (95% CI) of stroke by quintiles of magnesium intake, using multivariate Cox proportional hazard models, adjusting for potential confounders. Results: During 28 years of follow-up, 3237 total strokes (1664 ischemic, 544 hemorrhagic and 1029 probable/unknown) were documented. In multivariate analyses adjusting for age, total calories, smoking, body-mass index, parental history of heart disease, alcohol intake, physical activity, menopausal therapy, history of hypertension, hypercholesterolemia and diabetes at baseline, as well as use of multivitamin, aspirin, and thiazides, women in the highest quintile of magnesium intake had a relative risk (RR) of 0.85 (95% CI, 0.72 to 0.96; P for trend=0.03) for total stroke; 0.86 (95% CI, 0.72 to 1.01; P for trend=0.05) for ischemic stroke; and 0.85 (95% CI, 0.62 to 1.08; P for trend=0.37) for hemorrhagic stroke, compared with those in the lowest quintile. Further adjustment for potassium and calcium attenuated these associations; for total stroke the risk estimate was 0.90 (0.75 to 1.06; P for trend=0.38). Conclusions: Low magnesium intake may contribute to higher risk of stroke, but distinction from potential effects of potassium and calcium is difficult.

Intakes of Potassium, Magnesium, and Calcium and Risk of Stroke

We aimed to investigate the associations of dietary and total potassium, magnesium, and calcium intakes with stroke occurrence. A prospective cohort study was conducted among 36 094 participants aged 21 to 70 years. Dietary intake was assessed with a food frequency questionnaire. During 12 years of follow-up, 631 strokes occurred. After adjustment for confounders, magnesium intake was associated with reduced stroke risk (hazard ratio [95% confidence interval] per 100 mg/d, 0.80 [0.67-0.97] dietary magnesium; 0.78 [0.65-0.93] total magnesium). Potassium and calcium intakes were not associated with stroke. This study supports an association between high magnesium intake and a reduced stroke risk.

Dietary Magnesium Intake Is Inversely Associated with Mortality in Adults at High Cardiovascular Disease Risk1–3

The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55–80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com> as ISRCTN35739639.

Magnesium deficit - overlooked cause of low vitamin D status?

Like vitamin D deficit, magnesium deficit is considered to be a risk factor for cardiovascular disease. Several steps in the vitamin D metabolism, such as vitamin D binding to its transport protein and the conversion of vitamin D into the hormonal form 1,25-dihydroxyvitamin D by hepatic and renal hydroxylation, depend on magnesium as a cofactor. A new analysis of two National Health and Nutrition Examination Surveys data sets, published in BMC Medicine, investigated potential interactions between magnesium intake, circulating 25-hydroxyvitamin D, which is the generally accepted indicator of vitamin D status, and mortality. Data indicate a reduced risk of insufficient/deficient vitamin D status at high magnesium intake and an inverse association between circulating 25-hydroxyvitamin D and mortality, particularly cardiovascular mortality, among those with magnesium intake above the median. The study provides important findings concerning potential metabolic interactions between magnesium and vitamin D and its clinical relevance. However, results should be considered preliminary since biochemical data on individual magnesium status were lacking, confounding cannot be excluded and questions on the dose?response relationship still remain to be answered.Please see related research article: http://www.biomedcentral.com/1741-7015/11/187.

Dietary and Plasma Magnesium and Risk of Coronary Heart Disease Among Women

BackgroundMagnesium is associated with lower risk of sudden cardiac death, possibly through antiarrhythmic mechanisms. Magnesium influences endothelial function, inflammation, blood pressure, and diabetes, but a direct relation with coronary heart disease (CHD) risk has not been established.Methods and ResultsWe prospectively examined the association between dietary and plasma magnesium and risk of CHD among women in the Nurses' Health Study. The association for magnesium intake was examined among 86 323 women free of disease in 1980. Information on magnesium intake and lifestyle factors was ascertained every 2 to 4 years through questionnaires. Through 2008, 3614 cases of CHD (2511 nonfatal/1103 fatal) were documented. For plasma magnesium, we conducted a nested case–control analysis, with 458 cases of incident CHD (400 nonfatal/58 fatal) matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling. Higher magnesium intake was not associated with lower risk of total CHD (P‐linear trend=0.12) or nonfatal CHD (P‐linear trend=0.88) in multivariable models. However, magnesium intake was inversely associated with risk of fatal CHD. The RR comparing quintile 5 to quintile 1 of magnesium intake was 0.61 (95% CI, 0.45 to 0.84; P‐linear trend=0.003). The association between magnesium intake and risk of fatal CHD appeared to be mediated partially by hypertension. Plasma magnesium levels above 2.0 mg/dL were associated with lower risk of CHD, although not independent of other cardiovascular biomarkers (RR, 0.67; 95% CI, 0.44 to 1.04).ConclusionsDietary and plasma magnesium were not associated with total CHD incidence in this population of women. Dietary magnesium intake was inversely associated with fatal CHD, which may be mediated in part by hypertension.

High Dietary Magnesium Intake Is Associated with Low Insulin Resistance in the Newfoundland Population

BackgroundMagnesium plays a role in glucose and insulin homeostasis and evidence suggests that magnesium intake is associated with insulin resistance (IR). However, data is inconsistent and most studies have not adequately controlled for critical confounding factors.ObjectiveThe study investigated the association between magnesium intake and IR in normal-weight (NW), overweight (OW) and obese (OB) along with pre- and post- menopausal women.DesignA total of 2295 subjects (590 men and 1705 women) were recruited from the CODING study. Dietary magnesium intake was computed from the Willett Food Frequency Questionnaire (FFQ). Adiposity (NW, OW and OB) was classified by body fat percentage (%BF) measured by Dual-energy X-ray absorptiometry according to the Bray criteria. Multiple regression analyses were used to test adiposity-specific associations of dietary magnesium intake on insulin resistance adjusting for caloric intake, physical activity, medication use and menopausal status.ResultsSubjects with the highest intakes of dietary magnesium had the lowest levels of circulating insulin, HOMA-IR, and HOMA-ß and subjects with the lowest intake of dietary magnesium had the highest levels of these measures, suggesting a dose effect. Multiple regression analysis revealed a strong inverse association between dietary magnesium with IR. In addition, adiposity and menopausal status were found to be critical factors revealing that the association between dietary magnesium and IR was stronger in OW and OB along with Pre-menopausal women.ConclusionThe results of this study indicate that higher dietary magnesium intake is strongly associated with the attenuation of insulin resistance and is more beneficial for overweight and obese individuals in the general population and pre-menopausal women. Moreover, the inverse correlation between insulin resistance and dietary magnesium intake is stronger when adjusting for %BF than BMI.

Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = −0.009 mmol/L (95% CI: −0.013, −0.005), P < 0.0001] and insulin [−0.020 ln-pmol/L (95% CI: −0.024, −0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted.

Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies 1-4

Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 CHARGE consortium studies 1-4

Magnesium intake and risk of colorectal cancer: a meta-analysis of prospective studies

Epidemiologic studies have suggested that magnesium intake may be associated with a decreased risk of colorectal cancer (CRC), but the findings have been inconsistent. We aimed to assess this association by conducting a meta-analysis of prospective studies. We performed a literature search on PubMed database through July 2012 to identify prospective studies of magnesium intake in relation to CRC risk. Reference lists of the retrieved articles were also reviewed. A random-effects model was used to compute the summary risk estimates. Eight prospective studies containing 338,979 participants and 8000 CRC cases met the inclusion criteria. The summary relative risk (RR) for the highest vs lowest category of magnesium intake for CRC was 0.89 (95% CI, 0.79-1.00), with little evidence of heterogeneity. Restricting the analysis to six studies that have adjusted for calcium intake yielded a similar result. For colon and rectal cancer, the pooled RR was 0.81 (95% CI, 0.70-0.93) and 0.94 (95% CI, 0.72-1.24), respectively. In the dose-response analyses, the summary RRs for an increment of magnesium intake of 50 mg/day for colorectal, colon and rectal cancer were, respectively, 0.95 (95% CI, 0.89-1.00), 0.93 (95% CI, 0.88-0.99) and 0.93 (95% CI, 0.83-1.04), and there was some evidence of heterogeneity; omitting one study that substantially contributed to the heterogeneity yielded generally similar results, but with low heterogeneity. We detected no indication of publication bias. On the basis of the findings of this meta-analysis, a higher magnesium intake seems to be associated with a modest reduction in the risk of CRC, in particular, colon cancer.

High Dietary Magnesium Intake Decreases Hyperoxaluria in Patients With Nephrolithiasis

To examine the relationship between urine magnesium and hyperoxaluria in a cohort of patients with recurrent stone formation. A total of 311 patients with nephrolithaisis were evaluated. The patients were divided into quintiles of urine magnesium excretion, an accepted surrogate of dietary magnesium intake. Multivariate analysis was used to examine the relationship between magnesium and hyperoxaluria. The mean patient age was 50.0 ± 14.9 years, the body mass index was 28.0 ± 5.9 kg/m(2), and 130 were women and 181 were men. The mean urine magnesium excretion was 100.8 ± 42.0 mg/d (range 17.8-224.8). On multivariate analysis, an increasing quintile of urine magnesium was associated with decreasing hyperoxaluria (β = -0.37, 95% confidence interval -0.6 to -0.14, P < .05 for trend). When analyzed as separate quintiles with the lowest quintile of magnesium as the referent, only the greatest quintile demonstrated a statistically significant decrease in hyperoxaluria (β = -1.7, 95% confidence interval -2.7 to -0.7, P < .05 for trend). Increasing magnesium intake was associated with decreasing hyperoxaluria in this population of patients with stone formation. Our findings showed that high magnesium intake might be required to observe clinically significant effects from magnesium.

Magnesium intake and incidence of stroke: Meta-analysis of cohort studies

Background and aimsProspective cohort studies are inconsistent regarding the association between magnesium intake and the risk of stroke. The objective was to perform a meta-analysis to summarise the relationship between magnesium intake and risk of stroke in observational studies. Methods and resultsWe searched the PubMed and EMBASE databases for studies conducted from 1966 through August 2011. Prospective studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between magnesium intake and the risk of total stroke incidence or mortality were included. Data were independently abstracted by two investigators using a standardised protocol. Study-specific risk estimates were combined by using a random effects model.A total of eight studies, with 8367 stroke cases among 304,551 participants, were included in the meta-analysis. The summary RR indicated a significant association between the highest magnesium intake and reduced risk of total stroke (summary RR: 0.89; 95% CI: 0.82, 0.97); our dose–response analysis showed a borderline inverse association between magnesium intake and total stroke risk (an increment of 100 mg day−1; summary RR: 0.98; 95% CI: 0.95, 1.00). Subgroup analyses suggested a significant inverse association between highest magnesium intake and the risk of ischaemic stroke (summary RR: 0.88; 95% CI: 0.80, 0.98). ConclusionThe present meta-analysis of prospective cohorts suggests that higher magnesium intake is associated with reduced risk of total and ischaemic stroke. However, well-designed randomised controlled trials are needed to draw a definitive conclusion.

Magnesium Intake Is Not Related to Depression Risk in Spanish University Graduates1–3

AbstractMagnesium is the second most predominant intracellular cation and it is an important cofactor in over 300 enzymatic reactions. It is a calcium antagonist and a voltage-dependant blocker of the N-methyl-D-aspartate channel, which plays a role in the entrance of calcium into the neuron. Other mechanisms also add biological plausibility to neuro-protective properties for magnesium, including an inverse association with major depression. A higher magnesium intake has been related to lower depressive symptoms. However, epidemiological evidence on this issue is scarce. Our aim was to prospectively evaluate the association between dietary magnesium intake and depression incidence in a cohort of 12,939 Spanish university graduates initially free of depression (Seguimiento Universidad de Navarra Cohort Study). Total magnesium intake was assessed with a validated, semiquantitative FFQ and incident depression was ascertained through self-reports of a new clinical diagnosis of depression done by a medical doctor and/or the habitual use of antidepressive drugs. The self-report was validated against the Diagnostic and Statistical Manual of Mental Disorders(4th edition) criteria in a subsample of the cohort. Cox regression models were used to obtain HR of incident depression during follow-up according to baseline quintiles of magnesium intake using the lowest quintile as the reference category. After a median follow-up of 6.3 y, 737 new cases of depression were identified. No association between magnesium intake and depression was found, with multivariate-adjusted HR = 1 (reference), 1.00 (95% CI: 0.78–1.27), 1.00 (0.76–1.31), 0.95 (0.70–1.30), and 1.11 (0.77–1.59) for increasing categories (quintiles 1–5) of total magnesium intake. No dose-response relationship was found (P-trend = 0.59). Results were robust through different sensitivity analyses, including nutrient density or residual models. In conclusion, our findings do not suggest an inverse association between magnesium intake and depressive disorder.

Calcium, Magnesium, and Colorectal Cancer

To the Editor: High calcium consumption may confer a reduced risk of colorectal cancer.1,2 Dai and colleagues3 recently reported in a case-control study that intake of calcium may be associated with a decreased risk of colorectal adenoma only when the dietary calcium:magnesium intake ratio is low. This finding provides one possible interpretation for inconsistencies in previous studies of the association of calcium intake with risk of colorectal neoplasia.4 Belonging to the same family in the periodic table, calcium (Ca2+) and magnesium (Mg2+) share the same homeostatic control system and have the potential to antagonize each other physiologically.5 A high calcium intake reduces absorption of both magnesium and calcium,6 whereas moderate magnesium deprivation results in negative magnesium balance but increased calcium retention.7 Because of the potential competition between magnesium and calcium, we hypothesized that the dietary calcium:magnesium ratio may modify the effects of calcium supplementation on colorectal carcinogenesis. We sought to test this hypothesis using data from a randomized clinical trial of calcium supplementation (1200 mg/day), to prevent adenoma recurrence for a 4-year period. The outcome measure in this analysis was the recurrence of adenomas during the prespecified main risk period (ie, after a year-1 colonoscopy up to and including a year-4 examination).2 A validated semi-quantitative food frequency questionnaire (FFQ) was given at study entry to assess the usual diet. Consistent with our hypothesis,3 we found suggestions that the baseline dietary calcium:magnesium intake ratio modified the effect of calcium treatment on adenoma recurrence. Among subjects with the intake ratio above the median, calcium supplementation had no effect on the risk of one or more recurrent adenomas (relative risk [RR] = 0.98 [95% confidence interval (CI) = 0.75–1.28]) (Table). In contrast, among those with the baseline ratio less than or equal to the median, calcium treatment was associated with reduced risk (RR = 0.68 [95% CI = 0.52–0.90]; test for interaction, P = 0.075).Table: Effect of Calcium Supplementation on Recurrence of Total and Subtype Adenoma During Main Risk Period, Stratified by Median Baseline Calcium:Magnesium Intake RatioThe effect of calcium treatment did not differ by magnesium intake at baseline (test for interactions, P = 0.68). Previously, the study had shown that the effects of calcium supplementation on adenoma recurrence did not differ by baseline dietary intakes of calcium. We found no material change after adjustment for baseline dietary calcium intake. Thus, the suggestion of effect modification by the calcium:magnesium ratio cannot be attributed solely to the baseline dietary intake of either calcium or magnesium. Point estimates suggest that calcium reduces the risk of advanced adenoma regardless of the calcium:magnesium intake ratio level, a null finding that could be due to lack of statistical power. The effect of calcium on the risk of hyperplastic polyps did not differ by baseline calcium:magnesium intake ratio, but a protective effect of calcium on hyperplastic polyps was observed when baseline magnesium intake was below the median (test for interaction, P = 0.05) (eTable1, https://links.lww.com/EDE/A577). Although not entirely consistent, prospective studies conducted in Western societies have suggested that high intake of magnesium was associated with a reduced risk of colorectal cancer.8 Also, in a previous case-control study,3 polyp-free controls consumed substantially higher levels of magnesium than patients diagnosed with an initial colorectal adenoma. There are several possible reasons for the null magnesium finding in this study. It is possible that the association between magnesium intake and adenoma recurrence differs from that of an initial adenoma diagnosis. Also, baseline adenomas in participants with high dietary magnesium at entry may have occurred despite that intake, and so might develop adenoma recurrence along pathways unaffected by magnesium at that level. Future studies are needed to investigate the possibility that magnesium treatment among those with a high calcium:magnesium ratio at baseline could reduce the calcium:magnesium ratio and, in turn, reduce colorectal cancer risk. Qi Dai Department of Medicine Vanderbilt Epidemiology Center Vanderbilt-Ingram Cancer Center Vanderbilt School of Medicine Nashville, TN [email protected] Robert Sandler Department of Medicine University of North Carolina School of Medicine Chapel Hill, NC Elizabeth Barry Department of Community and Family Medicine Dartmouth Medical School Hanover, NH Robert Summers Department of Medicine University of Iowa Carver College of Medicine Iowa City, IA Maria Grau Department of Community and Family Medicine Dartmouth Medical School Hanover, NH John Baron Department of Medicine University of North Carolina School of Medicine Chapel Hill, NC Departments of Community and Family Medicine and of Medicine Dartmouth Medical School Hanover, NH

Abstract 4478: Erythrocyte magnesium, TRPM7 Thr1482Ile polymorphism, and colorectal adenoma risk

Abstract Background: Several epidemiologic studies indicate high intake of magnesium may be related to a reduced risk of colorectal cancer and adenoma. However, results from previous studies have not been consistent. We reported previously the inverse association between dietary magnesium and risk of colorectal adenoma primarily appeared in those who carried at least one Thr1482Ile allele in the transient receptor potential melastatin 7 (TRPM7) gene, which plays an essential role in the homeostasis and sensing of magnesium. Serum magnesium is regulated in a narrow range and previous studies indicate erythrocyte magnesium may be a better biomarker of body magnesium status than serum magnesium. Objective: To examine whether erythrocyte magnesium is associated with adenoma risk and if the association is modified by the Thr1482Ile polymorphism. Design: Included in this nested case-control study were 341adenoma cases and 343 matched polyp-free controls from the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. Total erythrocyte magnesium levels were measured using flame atomic absorption spectroscopy. Genotyping assay was performed using the TaqMan OpenArray platform. Multivariate logistic regression models were used to estimate the odds ratio and 95% confidence intervals as a measure of the strength of associations. The association of each genotype with colorectal adenoma risk was evaluated under dominant, recessive and additive models, respectively. Results: Overall erythrocyte magnesium level was not associated with risk of colorectal adenoma. However, erythrocyte magnesium tended to be associated with a reduced risk among those who carried at least one Thr1482Ile allele in the TRPM7 gene (rs8042919), particularly after adjusting for potential confounding factors, such as age, assay batch, family history, and dietary intakes of magnesium and fiber with the ORs (95% CI) of 0.19 (0.05, 0.76) and 0.34 (0.08, 1.49) respectively for the medium and highest tertile of erythrocyte magnesium levels versus the lowest tertile. In addition, among people with erythrocyte magnesium below the median, we found people who carried at least one 1482Ile allele tended to be at an elevated risk of adenoma with an OR (95% CI) of 1.7(0.85, 3.43), compared to those who did not carry the polymorphism; while the corresponding OR (95% CI) was 0.94 (0.49, 1.81) for those who carried at least one Thr1482Ile allele if erythrocyte magnesium was above the median. Conclusions: Our findings indicate the TRPM7 Thr1482Ile polymorphism may interact with erythrocyte magnesium levels in relation to colorectal adenoma risk even after controlling for dietary intake of magnesium. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4478. doi:1538-7445.AM2012-4478

Nutrient intake and risk of open-angle glaucoma: the Rotterdam Study

Open-angle glaucoma (OAG) is the commonest cause of irreversible blindness worldwide. Apart from an increased intraocular pressure (IOP), oxidative stress and an impaired ocular blood flow are supposed to contribute to OAG. The aim of this study was to determine whether the dietary intake of nutrients that either have anti-oxidative properties (carotenoids, vitamins, and flavonoids) or influence the blood flow (omega fatty acids and magnesium) is associated with incident OAG. We investigated this in a prospective population-based cohort, the Rotterdam Study. A total of 3502 participants aged 55 years and older for whom dietary data at baseline and ophthalmic data at baseline and follow-up were available and who did not have OAG at baseline were included. The ophthalmic examinations comprised measurements of the IOP and perimetry; dietary intake of nutrients was assessed by validated questionnaires and adjusted for energy intake. Cox proportional hazard regression analysis was applied to calculate hazard ratios of associations between the baseline intake of nutrients and incident OAG, adjusted for age, gender, IOP, IOP-lowering treatment, and body mass index. During an average follow-up of 9.7 years, 91 participants (2.6%) developed OAG. The hazard ratio for retinol equivalents (highest versus lowest tertile) was 0.45 (95% confidence interval 0.23–0.90), for vitamin B1 0.50 (0.25–0.98), and for magnesium 2.25 (1.16–4.38). The effects were stronger after the exclusion of participants taking supplements. Hence, a low intake of retinol equivalents and vitamin B1 (in line with hypothesis) and a high intake of magnesium (less unambiguous to interpret) appear to be associated with an increased risk of OAG.

Abstract A114: Dietary magnesium and calcium intake and risk of prostate cancer in Caucasian and African American men

Abstract Dietary magnesium intake is significantly less in African Americans than Caucasians. Deficiency of magnesium influences immune-inflammatory response and induces oxidative stress that leads to increased cell proliferation and DNA damage. Low magnesium level also increases the physiologic effects of calcium. Therefore, we hypothesize that low dietary intake of magnesium and high calcium intake will increase the risk of developing prostate cancer among African American men. To test this hypothesis, we conducted a pilot case-control study to determine whether deficiency of dietary magnesium and a high calcium intake are associated with an increased risk of prostate cancer. This study included 209 cases with histologically confirmed adenocarcinoma of the prostate (110 African American and 99 Caucasian men). 199 population-based controls were frequency matched by age (±5 years) and race. Risk factor questionnaire and nutrition data were collected via telephone interview. Dietary Assessment was performed using Modified Block-NCI Food Frequency Questionnaire with 129 food items, questions about restaurant intake and vitamin mineral supplementation. Dietary intake was calculated using DIETSYS + Plus version 5.9 dietary analysis program. Nutrition data for 166 cases and 155 controls were available for this analysis. Mean magnesium and calcium intake did not vary significantly between cases and controls. The odds ratios for magnesium was 0.79 (95% CI 0.39–1.61) and for calcium 1.35 (95% CI 0.87–2.09). However, among African Americans, the odds ratio for magnesium was 0.28 (95% CI 0.08–1.05) and for calcium 1.9 (95% CI 1.05–3.40). These preliminary data suggest that high dietary magnesium intake is inversely associated with prostate cancer, while higher calcium intake is associated with increased risk among African American men. These data may have significant public health implications since the identification of African American men deficient of magnesium can be targeted for preventive interventions. Results of this study needs to be confirmed in future studies with larger sample size. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A114.

Magnesium Intake and Risk of Type 2 Diabetes

OBJECTIVEEmerging epidemiological evidence suggests that higher magnesium intake may reduce diabetes incidence. We aimed to examine the association between magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies.RESEARCH DESIGN AND METHODSWe conducted a PubMed database search through January 2011 to identify prospective cohort studies of magnesium intake and risk of type 2 diabetes. Reference lists of retrieved articles were also reviewed. A random-effects model was used to compute the summary risk estimates.RESULTSMeta-analysis of 13 prospective cohort studies involving 536,318 participants and 24,516 cases detected a significant inverse association between magnesium intake and risk of type 2 diabetes (relative risk [RR] 0.78 [95% CI 0.73–0.84]). This association was not substantially modified by geographic region, follow-up length, sex, or family history of type 2 diabetes. A significant inverse association was observed in overweight (BMI ≥25 kg/m2) but not in normal-weight individuals (BMI <25 kg/m2), although test for interaction was not statistically significant (Pinteraction = 0.13). In the dose-response analysis, the summary RR of type 2 diabetes for every 100 mg/day increment in magnesium intake was 0.86 (95% CI 0.82–0.89). Sensitivity analyses restricted to studies with adjustment for cereal fiber intake yielded similar results. Little evidence of publication bias was observed.CONCLUSIONSThis meta-analysis provides further evidence supporting that magnesium intake is significantly inversely associated with risk of type 2 diabetes in a dose-response manner.

Dietary calcium and magnesium intake in relation to cancer incidence and mortality in a German prospective cohort (EPIC-Heidelberg)

To prospectively evaluate the associations of dietary calcium and magnesium intake with cancer incidence and mortality, data of 24,323 participants of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), who were aged 35-64years and cancer-free at recruitment (1994-1998), were analyzed using multivariate Cox regression models. After an average follow-up time of 11years, 2,050 incident cancers were diagnosed and 513 cancer deaths occurred. Dietary calcium intake was inversely but not statistically significantly associated with colorectal cancer risk (hazard ratio [HR] for per 100mg increase in intake: 0.95; 95% confidence interval [CI]: 0.88, 1.02) and lung cancer risk (HR for per 100mg increase in intake: 0.94; 95% CI: 0.87, 1.02). No statistically significant associations were observed between dietary calcium intake and site-specific or overall cancer incidence or mortality. Dietary magnesium intake was not statistically significantly associated with any of the investigated outcomes. This prospective cohort study provides no strong evidence to support that high dietary calcium and magnesium intake in the intake range observed in a German population may reduce cancer incidence or mortality.

Abstract 3758: The relationship of calcium and magnesium intakes, VDR polymorphisms and the risk of colorectal adenoma: results from the Tennessee Colorectal Polyp Study

Abstract Background: Epidemiological studies suggest that high calcium intake and adequate vitamin D levels may reduce risk of colorectal cancer or adenoma although findings have not been entirely consistent. Some previous studies found that the association between calcium intake and colorectal cancer or adenoma was modified by polymorphisms in vitamin D receptor (VDR) gene. In addition to regulating calcium level, vitamin D is also involved in magnesium homeostasis. However, no study has investigated possible interaction between magnesium intake and VDR polymorphisms. Objectives: To investigate whether intakes of calcium, particularly magnesium, interact with VDR genetic variants in relation to colorectal adenoma risk. Methods: Included in the study are 958 adenoma cases and 909 healthy controls from the Tennessee Colorectal Polyp Study (TCPS), an ongoing colonoscopy-based case control study conducted in Nashville, TN. Genotyping was performed using the Affymetrix Human Mapping 500K array set. Dietary nutrients intakes were obtained from food frequency questionnaire (FFQ) and dietary supplements and adjusted for total energy intake using the residual method. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Multiplicative interactions for gene-nutrients interactions were evaluated in logistic regression models by using likelihood ratio tests. Results: Eighteen tagging SNPs in the VDR gene were analyzed. Two SNPs (rs12717991, rs2189480) were significantly associated with a reduced risk of colorectal adenoma. Furthermore, intakes of calcium (p for interaction, 0.01) and magnesium (p for interaction, 0.03) significantly interacted with rs2189480 in relation to adenoma risk. The inverse association with rs2189480 was of borderline significance among participants with a low calcium intake (P for trend=0.06) with ORs (95% CI) of 0.80 (0.58, 1.10) and 0.67 (0.41, 1.10), respectively, for GT and TT. Among participants with high intake of magnesium, the inverse association was significant (P for trend=0.007) with ORs (95%CI) of 0.52 (0.38, 0.72) and 0.72 (0.44, 1.18), respectively for GT and TT. Conclusions: These findings suggest that some genetic variations in the VDR gene may interact with dietary intakes of calcium and magnesium intake in the risk of colorectal adenoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3758. doi:10.1158/1538-7445.AM2011-3758