Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis.

Magnesium (Mg) plays a key role in neurological functioning and manifestations. However, the evidence from randomized controlled trials (RCTs) and cohorts on Mg and cognitive health among adults has not been systematically reviewed. We aimed to examine the associations of various Mg forms (supplements, dietary intake, and biomarkers) with cognitive outcomes by summarizing evidence from RCTs and cohorts. PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for relevant peer-reviewed articles published up to May 3, 2024. Three random-effects models were performed, when appropriate, to evaluate the relationship between Mg and cognitive outcomes: 1) linear meta-regression, 2) non-linear (quadratic) meta-regression, and 3) meta-analysis using Mg variables categorized based on pre-existing recommendations. Three RCTs and 12 cohort studies were included in this systematic review. Evidence from the limited numbers of RCTs was insufficient to draw conclusions on the effects of Mg supplements. Cohort studies showed inconsistent dose-response relationships between dietary Mg and cognitive disorders, with high heterogeneity across populations. However, consistent U-shape associations of serum Mg with all-cause dementia and cognitive impairment were found in cohorts, suggesting an optimal serum Mg concentration around 0.85 mmol/L. This non-linear association was detected in meta-regression (Pquadratic = 0.003) and in meta-analysis based on the reference interval of serum Mg (0.75-0.95 mmol/L) [<0.75 compared with 0.85 mmol/L: pooled hazard ratio (HR) = 1.43; 95% confidence interval (CI) = 1.05, 1.93; >0.95 compared with 0.85 mmol/L: pooled HR = 1.30; 95% CI = 1.03, 1.64]. More evidence from RCTs and cohorts is warranted. Future cohort studies should evaluate various Mg biomarkers and collect repeated measurements of Mg intake over time, considering different sources (diet or supplements) and factors affecting absorption (e.g., calcium-to-Mg intake ratio). This systematic review was pre-registered in PROSPERO (CRD42023423663).

The interaction between estimated glomerular filtration rate and dietary magnesium intake and its effect on stroke prevalence: a cross-sectional study spanning 2003-2018.

Background: Despite the known associations of dietary magnesium intake and estimated glomerular filtration rate (eGFR) with cardiovascular diseases, their combined effects on stroke risk remain unclear. Therefore, this study aims to explore the associations of dietary magnesium intake and eGFR with stroke risk. Methods: The National Health and Nutrition Examination Survey (NHANES) data of 37,637 adult participants (≥18 years) from 2003 to 2018 was analyzed. Dietary magnesium intake was categorized as low (≤ 254 mg/day) and normal (> 254 mg/day) based on experimental data. Multiple logistic regression analyses and interaction tests were conducted to assess the associations of dietary magnesium intake and eGFR with stroke risk, with a focus on the interaction between different chronic kidney disease (CKD) stages based on eGFR levels and dietary magnesium intake. Additional analyses included multiplicative interaction analysis, restricted cubic spline analysis, and subgroup evaluations by age, sex, and ethnicity. Results: Dietary magnesium intake and eGFR were inversely correlated with the risk of stroke. Participants with low dietary magnesium intake had a higher stroke risk than those with normal magnesium intake (odds ratio [OR] 1.09, 95% confidence interval [CI]: 1.03-1.42). Likewise, low eGFR was associated with an elevated stroke risk compared with normal eGFR (OR 1.56, 95% CI: 1.15-2.13). Furthermore, the two factors showed a multiplicative interaction effect on stroke risk (OR 1.05, 95% CI: 1.01-1.09). We observed a significant interaction between stage G3 CKD and low dietary magnesium intake (OR 1.05, 95% CI: 1.01-1.09), suggesting a potential association with stroke risk. However, similar associations were not observed for stages G4 and G5, possibly due to the smaller number of participants with G4 and G5 CKD. The restricted cubic spline analysis revealed a non-linear relationship between dietary magnesium intake, eGFR, and stroke risk. The interaction between magnesium deficiency and low eGFR persisted in participants aged >60 years, as well as in females, non-Hispanic Black people, and people of other races. Conclusion: Dietary magnesium intake and eGFR correlate negatively with stroke prevalence. Moreover, there was an interaction between dietary magnesium intake and stroke prevalence across different CKD stages. Further large-scale prospective studies are needed to analyze the potential relationship between dietary magnesium intake, eGFR, and stroke.

Dietary Magnesium Intake in Relation to Depression in Adults: A GRADE-Assessed Systematic Review and Dose-Response Meta-analysis of Epidemiologic Studies.

CONTEXT: The relation of magnesium (Mg) intake with depression was previously investigated by meta-analyses. However, due to limited data, a dose-response analysis was not performed. OBJECTIVE: Considering the recently published articles, a systematic review and dose-response meta-analysis was conducted to summarize the relation of dietary Mg intake with depression in adults. DATA SOURCES: Medline (PubMed), ISI Web of Science, Scopus, and Google Scholar were comprehensively searched up to August 2023. DATA EXTRACTION: Observational studies that reported the relation of dietary Mg intake and depression in adults were included and their data were extracted. DATA ANALYSIS: A total of 63 214 participants from 10 cross-sectional and 3 cohort studies were included in the current study. Pooling 15 effect sizes from 12 studies (including 50 275 participants) revealed that individuals with the highest Mg intake had a 34% lower risk of depression, compared with those with the lowest Mg intake (RR: 0.66; 95% CI: 0.57, 0.78). Moreover, the linear dose-response analysis revealed that each 100-mg/d increment in Mg intake was associated with a 7% reduced risk of depression (RR: 0.93; 95% CI: 0.90, 0.96). Additionally, based on nonlinear dose-response analysis, increasing Mg intake from 170 to 370 mg/d was associated with a reduced risk of depression. Analyses were also conducted on 9 studies (49 558 participants) with representative populations, and similar results were found in the meta-analysis (RR: 0.71; 95% CI: 0.61, 0.83) and linear (RR: 0.93; 95% CI: 0.90, 0.96) and nonlinear dose-response analysis. CONCLUSION: The current study shows an inverse dose-dependent association between dietary Mg intakes and risk of depression in both a general and representative population of adults in a dose-response manner. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42024506570.

Association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event.

BACKGROUND: To test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event. METHODS: In this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999-2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event. RESULTS: We observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (ß=-0.01, [95% CI: -0.01, -0.00], P = 0.0440). CONCLUSIONS: Dietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Association between dietary magnesium intake and gallstones: the mediating role of atherogenic index of plasma.

BACKGROUND: Dyslipidemia and abnormalities in cholesterol metabolism are commonly observed in individuals with gallstone disease. Previous research has demonstrated that dietary magnesium can influence lipid metabolism. The atherogenic index of plasma (AIP) has emerged as a novel lipid marker. This study aimed to examine the possible correlation between dietary magnesium intake and gallstones and the potential mediating role of AIP in US adults. METHODS: A total of 4,841 adults were included in this study from the National Health and Nutrition Examination Survey (NHANES) conducted from 2017 to 2020. A variety of statistical techniques such as logistic regression, subgroup analysis, smoothed curve fitting, and causal mediation analysis were utilized to analyze the information collected from the participants. RESULTS: In the fully adjusted model, a statistically noteworthy inverse relationship was observed between dietary magnesium intake and the presence of gallstones, as indicated by an odds ratio (OR) of 0.58 and a 95% confidence interval (CI) of (0.42, 0.81). Causal intermediary analysis revealed that the association between magnesium intake and gallstones was partially mediated by AIP, with a mediation ratio of 3.2%. CONCLUSION: According to this study, dietary magnesium intake had a significant linear negative association with the prevalence of gallstones, in which AIP played a mediating role. This discovery offers novel perspectives on the prevention and management of gallstones.

The interaction between magnesium intake, the genetic variant INSR rs1799817 and colorectal cancer risk in a Korean population: a case-control study.

Magnesium may have a significant impact on the development of cancer. However, the relationship between magnesium intake and the risk of colorectal cancer (CRC) is unclear. Therefore, we evaluated the association between magnesium intake and the risk of CRC, and we investigated how the insulin receptor (INSR) rs1799817 variant impacts this relationship. Data from 1,420 CRC patients and 2,840 controls from the Korean National Cancer Centre were analysed. A higher intake of magnesium was associated with a reduced risk of CRC in the total population (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.81). We found that G + carriers of INSR rs1799817 with higher magnesium intake had a significantly lower risk of CRC (p for interaction = 0.003). Our findings indicated that high magnesium intake could be associated with a decreased risk of CRC, and this association could be modified by the INSR rs1799817 variant.

The Association Between Dietary Magnesium Intake and Pulmonary Function: Recent Fndings from NHANES 2007-2012.

This article aims to study the correlation between dietary magnesium intake and pulmonary function, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study examined representative samples of adults from the USA (n = 818; NHANES 2007-2012) to explore the correlation between magnesium intake and pulmonary function. We obtained the average magnesium intake over 2 days, as well as measured pulmonary function parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Weighted multivariable linear regression was used to investigate the relationship between magnesium intake and pulmonary function. Additionally, subgroup analyses, interaction tests, and sensitivity analyses were conducted. Weighted multiple linear regression models revealed a significant positive correlation between magnesium and pulmonary function, even after adjusting for all included confounding variables. When we categorized magnesium intake into tertiles, we found that participants in the highest tertile of magnesium intake had significantly higher values for FVC (ß: 898.54, 95%CI: 211.82-1585.25), FEV1 (ß: 858.16, 95%CI: 212.41-1503.91), FEV1/FVC (ß: 0.024, 95%CI: 0.004-0.044), PEF (ß: 1324.52, 95%CI: 481.71-2167.33), and FEF25-75% (ß: 831.39, 95%CI: 84.93-1577.84). Upon stratifying the data by age and sex, it was observed that this positive correlation was particularly pronounced among men aged 40-79. At the same time, the stability of the results was further confirmed by sensitivity analyses. This study suggested that dietary magnesium intake may improve pulmonary function.

The Association Between Dietary Magnesium Intake with Chronic Obstructive Pulmonary Disease and Lung Function in US Population: a Cross-sectional Study.

Chronic obstructive pulmonary disease (COPD) is now considered among the top three contributors to mortality globally. There is limited understanding surrounding the contribution of magnesium to the progression of COPD. This survey aims to evaluate the connection between dietary magnesium intake and both lung function and COPD prevalence among the US population. The research comprised 4865 participants in the National Health and Nutrition Examination Survey (NHANES) program conducted from 2007 to 2012. To evaluate the association between dietary magnesium intake and lung function as well as COPD, the study conducted multiple regression analyses, stratified analyses, and smoothed curves. In this study, we explored the relationship between higher magnesium intake and higher FEV1 [ß = 0.21 (95% CI 0.12, 0.30)] and FVC [ß = 0.25 (95% CI 0.14, 0.36)] after accounting for all potential confounding factors. We demonstrated a relationship between increased magnesium intake and reduced odds of developing COPD [OR = 0.9993 (95% CI 0.9987, 1.0000)]. The results of stratified analyses further indicated that the relationship between magnesium intake and the risk of COPD is more pronounced in the 40-60 age group and males. The study demonstrated positive associations between the intake of dietary magnesium and both FEV1 and FVC. Additionally, an adverse relationship between magnesium intake and the prevalence of COPD was also observed, suggesting that supplementation with magnesium may be a practical approach to preventing and managing COPD.

Adequate dietary magnesium intake may protect females but not males older than 55 years from cognitive impairment.

BACKGROUND: Magnesium is an essential nutrient required to maintain brain health throughout life, and adequate magnesium intake is positively associated with cognitive performance in older adults. However, sex differences in magnesium metabolism have not been adequately assessed in humans. OBJECTIVES: We investigated sex differences in the effect of dietary magnesium intake and the risk of different types of cognitive impairment in older Chinese adults. METHODS: We collected and assessed dietary data and cognitive function status in people aged 55 years and older in northern China who participated in the Community Cohort Study of Nervous System Diseases from 2018 to 2019 to explore the relationship between dietary magnesium intake and the risk of each type of mild cognitive impairment (MCI) in sex-specific cohorts of older adults. RESULTS: The study included 612 people: 260 (42.5%) men and 352 (57.5%) women. Logistic regression results showed that for the total sample and women's sample, high dietary magnesium intake reduced the risk of amnestic MCI (ORtotal = 0.300; ORwomen = 0.190) and multidomain amnestic MCI (ORtotal = 0.225; ORwomen = 0.145). The results of restricted cubic spline analysis showed that the risk of amnestic MCI (ptotal = 0.0193; pwomen = 0.0351) and multidomain amnestic MCI (ptotal = 0.0089; pwomen = 0.0096) in the total sample and women's sample gradually decreased with increasing dietary magnesium intake. CONCLUSIONS: The results suggest that adequate magnesium intake may have a preventive effect against the risk of MCI in older women.

Association of Magnesium Depletion Score with Congestive Heart Failure: Results from the NHANES 2007-2016.

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.

Dietary Magnesium Intake and Kidney Stone: The National Health and Nutrition Examination Survey 2011-2018.

BACKGROUND: The association between dietary magnesium intake (DMI) and kidney stone (KS) disease is not clear. AIM: To determine the association between DMI and prevalent KS disease defined as self-report of any previous episode of KS. METHODS: We examined The National Health and Nutrition Examination Survey (NHANES) 2011-2018 and used logistic regression analyses adjusting for demographics, BMI, histories of hypertension, diabetes, thiazide use, cigarette smoking, alcohol drinking, relevant dietary and supplemental intakes to determine the independent association between DMI and prevalent KS disease. RESULTS: A total of 19,271 participants were eligible for the final analysis, including 1878 prevalent KS formers. Mean DMI among stone formers was 295.4 mg/day, as compared to 309.6 mg/day among non-stone formers (p=0.02). Higher DMI was strongly associated with lower odds of prevalent KS disease in univariate analysis regardless of when DMI was analyzed as a continuous variable (OR=0.94, 95% CI: 0.89-0.99, p=0.02) or when the extreme quartiles of DMI were compared (OR=0.74, 95% CI: 0.60-0.92, p=0.007). In the multivariable-adjusted regression analysis, those in the highest quartile of DMI compared to the lowest quartile (≥379 mg vs. <205 mg) had significantly reduced odds of prevalent KS (OR=0.70, 95% CI: 0.52-0.93, p=0.01). When DMI was analyzed as a continuous variable, there was a trend toward reduced odds of prevalent KS disease with higher DMI (OR=0.92 per 100 mg, 95% CI: 0.84-1.01, p=0.07). CONCLUSIONS: Our study suggests that higher DMI is associated with a reduced risk of KS disease. Future prospective studies are needed to clarify the causal relationship between DMI and KS disease.

Dietary magnesium is able to influence the relationship between vitamin C and estimated glomerular filtration rate: A cross-sectional study.

The estimated glomerular filtration rate (eGFR) is a comprehensive index that is widely used to assess renal function. Although studies have confirmed a correlation between eGFR and dietary vitamin C, the impact of varying levels of vitamin C on eGFR remains unclear. Additionally, the interaction between dietary magnesium intake and vitamin C concentration on eGFR is not well understood. As such, the objective of this study was to investigate the relationship between dietary magnesium intake and vitamin C in relation to eGFR. This study analyzed the data of consecutive NHANES from 2005 to 2018. We included 17,633 participants aged 20 or older and used multiple linear regression analysis to evaluate the relationship between dietary vitamin C and eGFR. Dietary Mg intake from experimental data was dichotomized into a low dietary Mg intake group (≤254 mg/day) and a normal dietary Mg intake group (>254 mg/day). To evaluate the impact of dietary magnesium intake on eGFR, a multivariable linear regression was conducted utilizing an interaction test between dietary vitamin C and eGFR. We discovered a positive association between dietary vitamin C content and eGFR. The relationship between dietary vitamin C levels and eGFR differed between individuals with low Mg intake and those with normal Mg intake (ß: 2.96 95% CI:1.63 ~ 4.29 vs. ß: 1.05 95% CI: -0.15 to 2.25), and the positive association of high dietary vitamin C content with eGFR was stronger in the low Mg intake group. Furthermore, we observed that dietary magnesium intake significantly altered the positive association between dietary vitamin C and eGFR (interaction value of 0.020). Our experimental study revealed that the interaction between dietary magnesium and dietary vitamin C can significantly impact eGFR. This finding carries significant implications for the treatment of diseases resulting from abnormal eGFR, as well as the selection of clinically relevant drugs.

Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Relationship between short-term self-reported dietary magnesium intake and whole blood ionized magnesium (iMg2+) or serum magnesium (s-Mg) concentrations.

OBJECTIVE: Since we and others have shown that supplemental magnesium raises whole blood ionized magnesium (iMg2+) we investigated the relationships between self-reported dietary magnesium intake and concentrations of whole blood iMg2+ and serum magnesium (s-Mg). METHODS: We obtained whole blood iMg2+ concentrations, as well as s-Mg concentrations, from a pilot, three-arm, randomized, controlled, crossover bioavailability study of magnesium supplements (n = 23; 105 measures). Dietary magnesium intake was assessed using three-day food records and the Nutrition Data System for Research (NDSR, University of Minnesota, MN, USA). Whole blood iMg2+ was measured with an electrode analyser (NOVA Biochemical, Waltham, MA, USA), whereas s-Mg was measured using atomic absorption spectroscopy. A linear mixed-effects model was employed with dietary magnesium as the outcome variable and iMg2+, s-Mg, study treatment and study visit as fixed effects. We adjusted age, gender, race and body mass index covariates. RESULTS: Values for dietary magnesium, iMg2+ and s-Mg were 303.8 ± 118.9 mg/day, 1.3 ± 0.1 mg/dL and 2.2 ± 4.1 mg/dL, respectively. No association was found between dietary magnesium intake and iMg2+ -125 ± 176.95 (p = .49) or s-Mg -9.33 ± 5.04 (p = .08). CONCLUSIONS: Whole blood iMg2+ and s-Mg concentrations do not reflect short-term self-reported dietary intake in adults. Further research is needed to determine whether blood biomarkers of magnesium may reflect dietary magnesium intake.Key messagesDietary intake of magnesium, a shortfall nutrient, may be objectively measured using blood biomarkers of magnesium.Serum magnesium and whole blood iMg2+ were not associated with short-term dietary intake of magnesium.

The Association of Serum and Dietary Magnesium with Depressive Symptoms.

Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 mmol/L) on depression has not yet been investigated. We assessed the association between serum magnesium levels/dietary magnesium intake and depressive symptoms by analyzing nationally representative data from Taiwan (Nutrition and Health Survey in Taiwan, NAHSIT). We used the 5-item Brief Symptom Rating Scale to measure depressive symptoms. Subgroup analysis by sex was also performed. Serum magnesium levels had a low correlation with dietary magnesium intake. Higher serum magnesium levels were associated with lower depressive scores and a lower risk of depressive symptoms, but dietary magnesium intake showed no association. Sex differences were found. Compared with subjects with serum magnesium <0.75 mmol/L, those with ≥0.85 mmol/L had lower depressive scores. In conclusion, serum magnesium was inversely associated with depressive symptoms, but dietary magnesium intake was not. Subjects with CLMD showed similar depressive scores and were at a similar risk of depressive symptoms to those with serum magnesium < 0.75 mmol/L. CLMD should be considered while assessing the association between magnesium status and depressive symptoms.

Short-term dietary magnesium deficiency downregulates the expression of bone formation-related genes in rats.

Dietary magnesium deficiency increases osteoclastic bone resorption and decreases osteoblastic bone formation. Increased bone resorption due to dietary magnesium deficiency can be explained by increased expression of the receptor activator of nuclear factor kB ligand. However, the detailed mechanisms underlying decreased bone formation remain unclear. Thus, in the present study, to determine the mechanism underlying decreased bone formation induced by dietary magnesium deficiency, we investigated the effects of short-term dietary magnesium deficiency on the mRNA expression of genes related to bone formation in rats. Male Wistar rats were fed a control or magnesium-deficient diet for eight days. The mRNA expression level of Runx2, Sp7, Bglap, Alpl, Col1a1, Igf1, and Bmp2 in the femur was significantly lower in magnesium-deficient rats than in control rats. These results suggest that short-term dietary magnesium deficiency decreases the gene expression of insulin-like growth factor-1 and bone morphogenetic protein 2, which, in turn, decreases osteoblastic bone formation through the downregulation of osteoblastogenesis-related gene expression.

The Association between Dietary Magnesium Intake and Telomere Length in Adults with Hypertension.

BACKGROUND: Dietary micronutrients are significantly associated with telomere length, as shown in multiple studies. However, no study has investigated the association between magnesium intake and telomere length in adults with hypertension. METHODS: Participants were included from the National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2001-2002. Dietary magnesium intake was assessed using the 24 - hour recall method and the telomere length of leukocytes was measured using polymerase chain reaction (PCR). A multivariate regression model was then used to assess the association between dietary magnesium intake and telomere length in adults with hypertension. RESULTS: Our final analysis included 2199 hypertensive adults (46.79% males) with a mean dietary magnesium intake of 254.82±133.47 mg/day. Linear regression, adjusted for race, sex, age, smoking, uric acid, and other variables, showed that every 1 mg increase in dietary magnesium intake was associated with a 0.20 (95% CI: 0.01, 0.39, p = 0.043) longer telomere length in all participants. In the ≥45 years age group, there was a statistically significant association between the telomere length and dietary magnesium (95% CI: 0.16, 0.63, p <0.001). CONCLUSIONS: This study suggests that increased magnesium intake is associated with a longer telomere length in hypertensive adults, especially in those ≥45 years of age. However, further research is needed to determine a causal relationship.

Dietary magnesium and risk of cardiovascular and all-cause mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Background: An adequate intake of magnesium has been associated with lower risks of cardiovascular disease (CVD) and all-cause mortality in population-based studies. Whether an adequate magnesium intake is important for reducing long-term mortality risk after myocardial infarction (MI) is not yet clear. Objective: We examined magnesium intake in relation to CVD, all-cause and coronary heart disease (CHD) mortality, on top of drug treatment, in patients who had experienced an MI. Methods: We included 4,365 Dutch patients aged 60-80 y from the Alpha Omega Cohort with a history of MI <10 y before study enrollment. Dietary data over the past month were collected at baseline using a 203-item validated food frequency questionnaire from which magnesium intake was calculated. Patients were followed for cause-specific mortality through December 2018. HRs for mortality in tertiles of energy adjusted magnesium intake were obtained from multivariable Cox proportional hazard models, adjusting for age, sex, education, obesity and other lifestyle and dietary factors. Associations were also studied in relevant subgroups, including patients with diabetes and diuretics users. Restricted cubic splines were used for studying the continuous association of magnesium intake with CVD mortality. Results: The average magnesium intake was 302 ± 78 mg/day and 28% of male and 33% of female patients had adequate intakes. Magnesium containing supplements were used by 5.4% of the cohort. During a median follow-up of 12.4 years (48,473 person-years), 2,035 patients died, of which 903 from CVD and 558 from CHD. Higher magnesium intakes (>320 g/d), compared to the reference group (<283 mg/d), were associated with a lower risk of CVD mortality (HR: 0.72; 95% CI: 0.54-0.98) and all-cause mortality (HR: 0.78; 95% CI: 0.64-0.95) in the fully adjusted model. A non-significant inverse association was found for CHD mortality. Associations for CVD mortality were slightly stronger in diuretic users (HR: 0.55; 95% CI: 0.34-0.89). Results were similar after excluding magnesium supplement users. Conclusion: An adequate intake of magnesium may be important for lowering long-term mortality risk after MI, especially in patients treated with diuretics. The Alpha Omega Trial was registered at clinicaltrials.gov as NCT03192410.

Magnesium Status and Ca/Mg Ratios in a Series of Children and Adolescents with Chronic Diseases.

Magnesium (Mg) is an essential divalent cation involved in various enzymatic reactions that regulate vital biological functions. The main goal was to evaluate Mg status and its association with nutritional indicators in 78 children and adolescents with chronic diseases. We assessed anthropometric, biochemical, diet, body composition, and bone densitometry valuations. Serum Mg and Ca levels were determined using the standardized method and diet calcium (Ca) and Mg consumption by a prospective 72 h diet survey. Mean serum Ca (9.9 mg/dL), Mg (2.08 mg/dL) dietary Ca (102% DRI: Dietary Reference Intake), and Mg intake (105% DRI) were normal. A total of 45% had hypomagnesemia, 12% had hypermagnesemia, and 26% and 24% had inadequate and high Mg intake, respectively. Only 6% of patients had poor Mg intake and hypomagnesemia, and 54% and 90% of our series had an elevated serum Ca/Mg ratio > 4.70 (mean 4.79) and a low Ca/Mg intake ratio < 1.70 (mean 1.06), respectively. Both Ca/Mg ratios were linked with the risk of developing other chronic conditions such as cardiovascular disease, type 2 diabetes, syndrome metabolic, and even several cancers. Therefore, 79% of children and adolescents with chronic diseases were at elevated risk of having abnormal Mg status and developing other chronic illnesses.

Increased Wnt/ß-catenin signaling contributes to autophagy inhibition resulting from a dietary magnesium deficiency in injury-induced osteoarthritis.

BACKGROUND: Dietary magnesium deficiency, which is common in modern diet, has been associated with osteoarthritis (OA) susceptibility. Despite this clinical association, no study has addressed if dietary magnesium deficiency accelerates OA development, especially at molecular level. This study aimed to explore aggravating effects of dietary magnesium deficiency on cartilage damage in an injury-induced murine OA model and to determine the underlying mechanism. METHODS: Twelve-week-old C57BL/6J mice subject to injury-induced OA modeling were randomized into different diet groups in which the mice were fed a diet with daily recommended magnesium content (500 mg/kg) or diets with low magnesium content (100 or 300 mg/kg). Articular cartilage damage was evaluated using the OARSI score. To determine molecular mechanisms in vitro, mouse chondrocytes were treated with media of low magnesium conditions at 0.1 and 0.4 mM, compared with normal magnesium condition at 0.7 mM as control. Anabolic and catabolic factors, autophagy markers, ß-catenin, Wnt ligands, and a magnesium channel transient receptor potential cation channel subfamily member 7 (TRPM7) were analyzed by quantitative real-time PCR and immunoblotting. Autolysosomes were detected by DALGreen staining via fluorescence microscopy and autophagosomes were evaluated by transmission electron microscopy. Autophagy markers, ß-catenin, and TRPM7 were assessed in vivo in the mouse cartilage, comparing between dietary magnesium deficiency and normal diet, by immunohistochemistry. RESULTS: Dietary magnesium deficiency aggravated injury-induced cartilage damage, indicated by significant higher OARSI scores. Autophagy markers LC3-II and Beclin-1 were decreased both in low magnesium diet-fed mice and low magnesium-treated chondrocytes. The number of autolysosomes and autophagosomes was also reduced under low magnesium conditions. Moreover, magnesium deficiency induced decreased anabolic and increased catabolic effect of chondrocytes which could be restored by autophagy activator rapamycin. In addition, reduced autophagy under low magnesium conditions is mediated by activated Wnt/ß-catenin signaling. The expression of TRPM7 also decreased in low magnesium diet-fed mice, indicating that downstream changes could be regulated through this channel. CONCLUSIONS: Dietary magnesium deficiency contributes to OA development, which is mediated by reduced autophagy through Wnt/ß-catenin signaling activation. These findings indicated potential benefits of adequate dietary magnesium for OA patients or those individuals at high risk of OA.