Background: Magnesium plays an essential role in the synthesis and metabolism of vitamin D and magnesium supplementation substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets. We hypothesized that dietary magnesium alone, particularly its interaction with vitamin D intake, contributes to serum 25-hydroxyvitamin D (25(OH)D) levels, and the associations between serum 25(OH)D and risk of mortality may be modified by magnesium intake level. Methods: We tested these novel hypotheses utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2006, a population-based cross-sectional study, and the NHANES III cohort, a population-based cohort study. Serum 25(OH)D was used to define vitamin D status. Mortality outcomes in the NHANES III cohort were determined by using probabilistic linkage with the National Death Index (NDI). Results: High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency. Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin D insufficiency. Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median. Conclusions: Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium. Future studies, including cohort studies and clinical trials, are necessary to confirm the findings.

Background: Mean magnesium intake in the US population does not differ from that in East Asian populations with traditionally low risks of colorectal cancer and other chronic diseases, but the ratio of calcium to magnesium (Ca:Mg) intake is much higher in the US population. Transient receptor potential melastatin 7 (TRPM7) is a newly found gene essential to magnesium absorption and homeostasis. Objective: We aimed to test whether the association of colorectal polyps with intake of calcium, magnesium, or both and Thr1482Ile polymorphism in the TRPM7 gene is modified by the Ca:Mg intake. Design: Included in the study were a total of 688 adenoma cases, 210 hyperplastic polyp cases, and 1306 polyp-free controls from the Tennessee Colorectal Polyp Study. Results: We found that total magnesium consumption was linked to a significantly lower risk of colorectal adenoma, particularly in those subjects with a low Ca:Mg intake. An inverse association trend was found for hyperplastic polyps. We also found that the common Thr1482Ile polymorphism was associated with an elevated risk of both adenomatous and hyperplastic polyps. Moreover, this polymorphism significantly interacted with the Ca:Mg intake in relation to both adenomatous and hyperplastic polyps. The subjects who carried ≥1 1482Ile allele and who consumed diets with a high Ca:Mg intake were at a higher risk of adenoma (odds ratio: 1.60; 95% CI: 1.12, 2.29) and hyperplastic polyps (odds ratio: 1.85; 95% CI: 1.09, 3.14) than were the subjects who did not carry the polymorphism. Conclusion: These findings, if confirmed, may provide a new avenue for the personalized prevention of magnesium deficiency and, thus, colorectal cancer.

Urinary metals are considered measures of long-term exposures of metals, such as cadmium (Cd). Some studies indicate reduced renal function may affect the urinary excretion of several metals in general population making assessments difficult. To examine whether reduced renal function is associated with reduced urinary excretion of 12 metals or their metabolites and, in turn, an underestimated measure of Cd in general population. We conducted analyses using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2012. Multiple linear regression models were used to examine the associations between urinary metal levels and estimated glomerular filtration rate (eGFR). Restricted cubic spline regression models were used to evaluate the nonlinearity. Urinary metal levels significantly increased (p < 0.001) with increasing eGFR, except for antimony (p = 0.172). Urinary levels of arsenic, dimethylarsonic acid, cobalt, molybdenum and tungsten increased linearly with eGFR, while Cd, lead, mercury, barium, cesium and thallium increased nonlinearly (p < 0.001) with eGFR. Based on a restricted cubic spline regression model, we found, corresponding to a fixed blood Cd adverse cutpoint of 5 μg/L, predicted urinary Cd cutpoints substantially varied from 0.78-1.21 μg/g for urinary Cd between those aged <40 years and who had chronic kidney disease and those aged 60 years or over with normal renal function, respectively. Reduced renal function is associated with reduced urinary metals; and associations are also observed across the eGFR range not just in the reduced range. Urinary abnormal cutpoints of metals are likely dependent on eGFR and age. The associations between urinary exposure of metals and disease risk are likely underestimated without considering the modifying effect of renal function.

Objectives Magnesium (Mg) and calcium (Ca) antagonise each other in (re)absorption, inflammation and many other physiological activities. Based on mathematical estimation, the absorbed number of Ca or Mg depends on the dietary ratio of Ca to Mg intake. We hypothesise that the dietary Ca/Mg ratio modifies the effects of Ca and Mg on mortality due to gastrointestinal tract cancer and, perhaps, mortality due to diseases occurring in other organs or systems. Design Prospective studies. Setting Population-based cohort studies (The Shanghai Women's Health Study and the Shanghai Men's Health Study) conducted in Shanghai, China. Participants 74 942 Chinese women aged 40–70 years and 61 500 Chinese men aged 40–74 years participated in the study. Primary outcome measures All-cause mortality and disease-specific mortality. Results In this Chinese population with a low Ca/Mg intake ratio (a median of 1.7 vs around 3.0 in US populations), intakes of Mg greater than US Recommended Daily Allowance (RDA) levels (320 mg/day among women and 420 mg/day among men) were related to increased risks of total mortality for both women and men. Consistent with our hypothesis, the Ca/Mg intake ratio significantly modified the associations of intakes of Ca and Mg with mortality risk, whereas no significant interactions between Ca and Mg in relation to outcome were found. The associations differed by gender. Among men with a Ca/Mg ratio >1.7, increased intakes of Ca and Mg were associated with reduced risks of total mortality, and mortality due to coronary heart diseases. In the same group, intake of Ca was associated with a reduced risk of mortality due to cancer. Among women with a Ca/Mg ratio ≤1.7, intake of Mg was associated with increased risks of total mortality, and mortality due to cardiovascular diseases and colorectal cancer. Conclusions These results, if confirmed, may help to understand the optimal balance between Ca and Mg in the aetiology and prevention of these common diseases and reduction in mortality.